In 1971, John List left a note with the bodies of his mother, wife, and three children in his mansion ballroom, funeral organ music blaring from a central sound system, and disappeared. Eighteen years later, all detectives had to work from is an outdated photograph of List. In 1989, the popular television series America's Most Wanted commissioned an age-scaled bust of List to aid viewers in identifying the confessed murderer. Dr. Frank Bender, nationally-recognized artist and sculptor, worked with forensic psychologist Richard Walter to develop a profile of the aging List.

In 1992, in a rural Canadian community, Dr. John Schneeberger is accused of sedating and sexually assaulting two of his female patients. DNA tests show him to be innocent, but the women persist with their claims; 7 years later, a private investigation leads to a surprising discovery.

When court clerk Peter Porco doesn't report to his work in November 2004, a courts officer is ordered to the Porcos' family home in Bethlehem, NY. Inside the home, he finds murdered Peter Porco and his barely alive wife Joan who had both been savagely attacked with a fireman's axe. Eventually, a DNA sample may lead to the killer.

Joshua Ford and Martha Crutchley spent Memorial Day weekend at the beach, and then they simply vanished. A week later, police would get an unexpected lead from a robbery in progress, and the evidence they found helped solve a crime of unparalleled violence and brutality.

In 1989, the bodies of Joan Rogers and her two teenage daughters were found floating in Tampa Bay. The water washed away any evidence, but police hoped a handwritten note found in the victims' car would lead to the killer, so they posted huge copies of the note on five highway billboards.

Haunted by the disappearance of her mother some twenty years earlier, a young woman undertook an investigation of her own. Her mother's diary was in the now cold case file; there, in her mother's own handwriting, she discovered a dark family secret, which might have been the reason her mother vanished.

A young man was killed in a mysterious car crash, but the evidence at the scene led investigators to believe it was not an accident. Forensic science revealed what really happened, and the truth devastated three families.

A 6-year-old girl ran and hid when she saw her grandmother being beaten to death, but the man followed her, beat her and assaulted her. The girl said he was her Uncle Clarence, and he was convicted because of her identification. She recanted her testimony years later, but the court denied Clarence's petition for a new trial. His wife was convinced he was innocent, and decided to conduct her own investigation to prove it.

A bullet-riddled car, a missing driver, and no witnesses. Was this an ambush or a random attack? Had the victim been abducted or was she dead? The answers lay in a unique clue so tiny it was measured in millionths of a meter.

On December 10, 2003, a gunman opened fire as a family of four entered their home, killing two and wounding the others. He’d pulled open a few drawers to make it look like a robbery, but the scene was clearly staged. When police pieced together the clues, they discovered an unlikely suspect and a carefully orchestrated plot.

In 2003, Tiffany Rowell and three of her friends were brutally murdered in their affluent Clear Lake, TX, neighborhood and the crime scene yielded little evidence. The next-door neighbors had seen two young people dressed in black walking nearby and their descriptions were used to create composite drawings, which become a key element in solving the crime.

Two people in Seattle, Washington died after taking an over-the-counter pain reliever; lab analysis of the pills showed they were tainted with a lethal concentration of cyanide. The investigation which followed led police to a suspect with a motive for murder and a callous disregard for others.

When a decomposed body is discovered inside a barrel, police immediately suspect foul play. But the body had been placed there 30 years earlier. One of the few clues was an address book found along with the body but years of moisture had washed away the ink. Scientists desperately searched for a way to unlock the secrets of that address book.

In 1994, a human skull found in an Ohio pond uncovers a ghastly crime. Markings on the skull indicate that the victim had been stabbed many times and that the teeth had been removed with needle-nose pliers in an attempt to keep the victim's identity a secret. Forensic scientists use DNA matches to indentify the skull.

The body of a young California co-ed was found under an isolated ramp of the Interstate, and San Diego police had no idea who would want this girl dead. But their questions would be answered when they discovered a tiny, unique fiber on the victim's clothing, which led them straight to the most unlikely of killers.

Two men were convicted of intentionally shooting and killing a passenger in a moving car, their friend was granted immunity for testifying against them, and the case was closed. Then a bomb exploded in the family home of the state's witness, instantly killing his father. Investigators turned to forensic science, hoping to determine if this was an act of revenge and if there was a way to link the two deadly crimes.

In 2005, David Castor suffered a slow, agonizing death over a period of days. His wife Stacey maintained it was suicide, even though it was done with antifreeze. Police were skeptical, especially when they learned Stacey's first husband Michael Wallace died when he was only 38 years old and she refused to consent to an autopsy.

The first case to use DNA evidence is detailed. In 1983 Leicester, England, police were stymied by a rape/murder of a 15-year-old girl; three years later, faced with a similar crime, they turned to Dr. Alec Jeffreys, a molecular biologist with a revolutionary approach to solving the case.

The year was 1984, and a serial killer was on the loose in Florida. Eight women had been found dead. At each crime scene, investigators found tiny red fibers, fibers they hoped would lead them to the killer.

Creating a “profile” of a serial killer is part science and part intuition. The science involves studying criminals who have committed similar crimes, to see what characteristics they have in common. In a search for the killer of two teenagers in Texas, a behavioral profile led to a possible suspect - and hard science proved the profile was correct; it shows a behavioral study on how most serial killers also have a history of abusing animals.

For six years, a serial killer prowled the streets of New York City. He wrote letters to police and The New York Post, indicating he would kill twelve people, one for each astrological sign.

In 1984, California firefighters had battled ten arson fires in three weeks. When cigarettes and a scrap of paper connected the southern California fires to several fires further north, the hunt was on for a dangerous pyromaniac. Investigators finally found a fingerprint, and it pointed to a most unlikely suspect.

A two-man shrimp boat sank when a fast-moving, violent storm struck the Louisiana coast. The captain drowned, and the deckhand was rescued fourteen hours later. He told the Coast Guard that the captain's foot had become entangled in the fishing nets; they tried frantically to free him, but they failed. The deckhand was considered a hero until the captain's body was found. Eventually, the public discovers that he was coerced into confessing to the captain's murder.

Bombings are difficult to solve, because the perpetrator isn't usually at the scene, and the evidence goes up in smoke. But there are clues if investigators know where to look. In this case pieces of plastic the size of grains of sand, held the key to a man's murder.

When a fire destroyed most of a home and a young boy went missing, police organized the largest search in the history of their small town. First the boy's backpack was discovered five miles from home, and then his body was found 50 miles away. But the killer had been careless, and the evidence he left behind would lead police directly to him.