In the Brighton Beach area of New York City, a man named Yaponchik kills a Russian Elder by shooting him in the face with a 12 gauge pistol. It becomes the third such killing in which the perpetrator mutilated the body to prevent positive identification. Frank assists N.Y.P.D. Lieutenant McCormick, Yura Surova, from the Moscow Police Department, and undercover officer Andrei Medikov with the investigation. While inspecting the Elder's corpse, Frank notices an odd mark in the shape of a inverted "V." But he is unable, at first, to determine its meaning.

Maddie Haskel, twenty-years-old and heartland pretty, attends her mother's funeral in Joplan, Missouri. After the service, Maddie returns to her family's home, where she is approached by a vicious-looking man named Jim Gilroy. Gilroy's attempt to rape Maddie comes to a sudden halt when Maddie's boyfriend, Bobby Webber, emerges from the shadows wielding a length of iron pipe. After Gilroy is knocked unconscious, Bobby and Maddie drive off into the night with their prisoner safely tucked away in the trunk of their automobile. A Missouri State Trooper notices the vehicle has a burned-out tail light and orders Bobby to pull over. When the trooper hears noises emanating from the trunk, Bobby grabs a .357 and shoots and kills the trooper.

Frank searches for a female serial killer and her lover after the pair escape from prison.

Near the University of Colorado at Boulder, a group of college-age students gather at a warehouse/techno night club. Art Nesbitt, a pharmacist, approaches a couple, Mel and Leslie. He opens his palm, revealing two capsules. Under the influence of the powerful drugs, the couple accompany Nesbitt to a small room. Nesbitt captures their lovemaking on videotape, then injects them with a lethal poison.

In Manhattan, Frank Black and an anthropologist link a bizarre, ritualistic slaying to a lost tribe of Native Americans who follow apocalyptic prophecies.

Catherine and Lara investigate when five girls claim they saw a vision of the Virgin Mary.

Emma tries to help her drug addicted sister and learns that local addicts are exhibiting strange mutations linked to tainted heroin.

Millennium Group offender profiler Frank Black investigates the abduction of a bus full of schoolchildren, requiring the help of fellow Group members Peter Watts and Lara Means as he tracks a man preparing for a third world war.

Asylum inmates become prime suspects in a series of murders linked to an urban legend.

A mysterious Asian woman is linked to several strange deaths aboard a ship.

A fundamentalist Jewish sect abducts a pregnant woman hoping to raise a pure child for the priesthood and force the coming of the Messiah.

Emma and Frank investigate the mysterious biological research conducted by a former Millennium Group member who is dying from a mysterious disease.

Frank and Watts travel to Germany where they seek a legendary Holy relic.

Frank aids in the search for a man who is supposedly carrying a highly contagious virus and discovers the secret behind the Human Genome Project.

Frank senses that Bletcher's killer is responsible for the disappearance of a teenaged boy.

Four devils gather at a doughnut shop and swap stories about their dealings with mankind.

Frank and Emma investigate murders on the set of a movie based on one of Frank's former cases.

Against the initial resistance of the Group, Frank travels to Portland, Oregon, to investigate a murder at an animal shelter. He meets with Jim Horn, a profiler and candidate for the Millennium Group. But Horn is distracted by his imminent divorce, and there is tension between him and Frank. When the killer strikes again, Horn is losing control, and Frank not only has to catch the killer who leaves grisly messages on his victims, but he has to contend with Horn as well who is more than ready to stop the murderer with terminal prejudice.

A desperate man sets out on a killing spree taking revenge on the holy men that he believes have led him to stray. Frank can see the man's sense of faith and the lack his faith could be the key to stopping this killer. Frank then puts himself in danger when he walks into a hostage situation at a small town church.

An unidentified man in a van follows a teenage boy, Josh Comstock, as he rides his new motorcycle through Vista Verde Estates, a gated, upper middle-class neighborhood in Washington State. As night falls, Josh rides his bike across the dirt of an undeveloped cul-de-sac. The driver parks his van and approaches the boy, suddenly, jabbing a cattle prod into Josh's chest and sending him flying backwards into the dirt. When Mr. and Mrs. Comstock awaken the next morning, they find the corpse of another teenage boy in Josh's bed--and their son missing.

Frank's brother, Tom, and his wife, Helen, travel to Seattle where they hold their newborn son's baptism. After the ceremony, Frank checks up on Jordan, who is off playing with a friend inside the church. He finds his daughter huddled in a ball on the pew, clutching herself. She speaks of a man she saw hurting her Aunt Helen. Frank rushes outside the church. He finds his baby nephew unharmed in the back seat of Tom's rental car, but notes a blood droplet on the infant's face. Frank and Tom realize Helen was abducted.

In rural Arkansas, Frank investigates the owner of a daycare center accused of child abuse, only to be accused himself.

Serial murders in the guise of assisted suicides stymie Frank, whose primary suspect is a charismatic hospice nurse. Frank and Lara investigate to determine if it is murder.

As the schism between the two warring Millennium Group factions deepens, Frank discovers the existence of yet another player in the power struggle.

The Marburg virus has apparently run its course. Several months after the death of his wife and a nervous breakdown, Frank rejoins the FBI and investigates a plane crash with a new partner.