Dr. Campbell is asked to write an endorsement for a new book about female heart health written by a friend and patient. After the author dies of a heart attack, her husband refuses to publically announce her cause of death because he fears it would hurt sales of the book even though her diet had nothing to do with her death (she had heart disease). Lu is shocked when three high school girls come into the ER with similar and shocking symptoms that point towards poisoning.

Lana bets her pink feather pen that she'll sign up more people than a friend will for the Rittenhouse Breast Cancer Walk. She faces some difficulties, however, and goes to extreme measures to get people to sign up. Lu tells a teenaged patient that she is pregnant and she in turn tells Lu that Lu's son Marc is the father. In a shocking ending, the girl reveals a horrifying secret. Andy, meanwhile, takes action when Lizzy's friends receive ""fat letters"" and instead makes the school food healthier when Lizzy starts to severely diet.

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Lu copes with the trauma of being raped by devoting her thoughts to a patient who accidentally overdosed on over-the-counter cough medicine. Dana, meanwhile, grudgingly turns to Dr. Kilner for advice about a pregnant woman with colon cancer.

An estranged sister must work up the courage to ask her Olympic gymnast sibling to donate her liver to save her life. Andy and Kayla help a clinically depressed and struggling resident get back on track after a suicide attempt. Lu tries to convince Jonas not to build a large discount multi-purpose store in her neighborhood as it would close down many of the mom and pop stores that had been there for years.

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Andy finds out that a TV chef has leperachy when she develops a rash. Lu must decide between avenging Mickey's death and her own beliefs about the death penalty and honesty when she is asked to testify in the defense of his murderer who clearly is mentally unstable. Lu also is shocked when she discovers her neighbor's body and corruption in the Philadelphia Police Department.

As a heat wave hits Philadelphia, Andy & the staff will need to get used to its disaster plan to cope with heat wave. Claire a patient of Dr. Campbell is told she will develop Alzheimer's disease within 10 years, she also wants to have a baby. Andy & tells her kids about Dr. Morton, her kids question why she can't make time for kids. Clare worries that her kids might have the gene PGD (the gene that leads to finding Alzheimer's early.) A young girl with Down's Syndrome tells Lu she shot a girl to get in a gang. The mother later tells Lu that she had her 16 year old (with Downs Syndrome) confess to the crime to protect her sister who actually committed the crime.

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Dr. Campbell's husband hits her and she kicks him out of their house.

In a surprise twist following the suspenseful season finale cliffhanger, Mickey jumped in front of Lu and took the bullet for her; saving her life. Lu quickly rushes him to the hospital but little can be done to save his life besides putting him on a respiratory machine. Andy and Bob try to convince Lu to take him off the respirator. While Lu deals with the emotional trauma of Mickey's death, Andy tries to perform an experimental procedure on a baby in a bubble but is interrupted by Bob with news that the FDA has un-approved the procedure. Meanwhile Andy gets herself into a bureaucritical battle when she tries to get a patient who has no health insurance a free heart transplant. Also, Andy must tell Lizzy and Jesse that she and Les are getting a divorce and that he is moving across the country.

An Indian heiress with a deformity turns to Andy for treatment so that her parents can arrange a marriage for her. Things get complicated when the woman realizes that she will lose the freedoms she has been afforded because of her imperfection. Also, Lu helps an older woman with Alzheimer's use her past for her own benefit. Meanwhile, Andy counsels a young woman who is seeking ""revirginization"" surgery.

On a stormy Halloween night, a 7 year old girl suffers a serious burn while trick or treating and the only person who could possibly save her life by giving her a skin transplant is her twin sister. Lu must decide if it is ethical to ask the young girl to proceed with such a risky and painful procedure. Meanwhile, Lizzy and her friends witness a crime in the hospital morque while Peter and Lana get the hospital into the Halloween spirit.

A pregnant and very ill pro-life politician has her principles put to the ultimate test when the only treatment that will save her life will result in losing her baby. Meanwhile, a patient of Lu's who is trying to pass herself off as a much younger woman is hampered by the inconvenient arrival of menopause.

Lu faces the doctor that raped her when he needs surgery that can save his life. Peter goes out with a woman who has terminal diabetes.

Kayla is frustrated when a patient refuses to let her treat her due to her race and her intern status. Andy refuses to treat her and insists that Kayla handles the patient. A complaint is filed against Andy because she refused to treat the patient. A new doctor at Rittenhouse must take over Milo's patients and replace him in the hospital.

Lu treats a young patient with Bi-Polar disease which causes her to act hazardously violent. Her mother must decide whether to keep her or give her up to a mental institution. Meanwhile, Andy helps a woman have an invitro fertilization. She uses new technology to help the couple have a boy because of a genetic female-only disease in the family but later a web of lies and deceivements is revealed. Peter gets jealous when Kayla dates a man he volunteers for at a zoo.

Lu and Andy treat 3 patients that have similar symptoms but seem to have nothing in common. Meanwhile, Andy must meet face-to-face with the drunk driver who killed Milo. Andy is horrified when Jesse befriends him after he gives a speech about the dangers of drunk driving at her school. Meanwhile, Jonas is investigated for insider trading. Later, in a shocking climax, Jesse is in a drunk driving accident.

Philadelphia baseball fans blame Dana when the home team loses a crucial playoff game. Lu cares for a piano prodigy with scleroderma, a potentially fatal disease that hardens the body's organs. Peter helps a retired research chimp find greener pastures.

Lu treats a patient who may SARS the doctors tell patents about SRS as they wait for the lab tests. Ben comforts a patient. Andy worries that she will lose Jesse if she moves to California.

Andy tells a famous rock star and a patient to rest and cancel some of her concerts because of fatigue. The rock star invites Lu's young patient who has a terminal disease to spend the day with her. Lu's patient's mother directs a terrible accusation at the rock star. Ben starts a concierge service to keep the clinic open after it faces financial difficulties.

Dr. Campbell treats a patient for what she believes is alcoholism but she won't admit to her drinking problem. The patient's daughter goes to desperate measure to get her mom to stop drinking. Another of Andy's patients needs to get a kidney transplant but nobody in her family is a match. Tammy's mom then reveals a horrible secret that could save her daughter's life. Meanwhile, Lu, Lana, Peter, and Ben go out on the streets to find out what is threatening the lives of young infants.

Andy worries about a patient who continues to ask for surgery to make her breasts perfect even after she has had many surgeries. Andy warns her patient that if she continues to have more surgery she could make it harder for machines to detect a possible sign for breast cancer due to the fact that she has a lot of scar tissue. Andy believes her patient may have a body-image disorder and is worried that her patient could go to extreme measures to improve her body image. Lana's computer breaks down with Marc's thesis on it and Lana, Peter, Ben, Lu, and him must pull an all-nighter to get it done and get the thesis done and turned in in time. Lu must say good-bye when Ben is transferred to Miami and Marc goes away to college.

After a councilwoman comes to the clinic to see Dr. Dana Stowe, Lu Delgado is trying to get gang members who are angry at the Councilwoman because they are unable to get insurance. The gang members continue arguing with the councilwoman who isn't interested in what they have to say. Seconds later an unknown gunmen began shooting at the clinic and Dana's patient is accidentally shot and is in need of immediate medical attention. The operation helps Dana's patient learn a valuable lesson. Also in this episode, Peter treats a woman who goes berserk at the shooting in the clinic. He later finds that she grew up in Cambodia during the war. But she may be suffering from more than pain from the memories.