Investigar os fatos após um crime ou um assassinato, significa entrar na mente do executor. Mas quando a vítima desaparece sem deixar rastros, a investigação é muito mais desafiadora. O trabalho requer a desconstrução da pessoa que está desaparecida e a construção de seus últimos momentos conhecidos. É aí que o brilhante trabalho da equipe do FBI de 'Pessoas Desaparecidas' de NY começa. Essa força especial é liderada pelo agente Jack Malone, que usa de conhecimentos avançados de psicologia. No time de Malone estão a bela Samantha, a brilhante Vivian, o apaixonado Danny e o novato Martin. Juntos eles buscam pistas para descobrir o que ocorreu com as vítimas desaparecidas. Eles reconstroem o 'Dia Do Desaparecimento', focando em cada detalhe e em cada minuto das últimas 24 horas antes do misterioso desaparecimento.
Bryan Parker is questioned by the FBI after being found alone on the road by a police officer, his hand bandaged. He tells them about a young boy his father had abducted, and soon the team is searching for Todd. The search initially goes nowhere, and Sam continues to question Bryan, but they get a lead when Bryan identifies a snapshot of the boy that reveals his identity to be that of missing boy Daniel Ellison. It isn't long before the squad realises that Daniel isn't the first boy that Parker grabbed, and follow his past to find him and the missing boy.
Cindy Peterson, a mother who had become a stripper to support her family, goes missing after work one night, and Jack sends Elena in undercover at the strip club to learn what she can. Danny moves in to keep an eye on her after someone catches on to her spying, while Vivian discovers that Jim Peterson hasn't been completely honest with them. Jack faces censure from Olczyk over his relationship with Ann, and is angry with Ann after she admits to him that she thinks he let their relationship cloud his judgment in the Davis investigation.
The team investigates when Malia Norton, a teenager at a detention center, disappears after being threatened by one of the other residents. Malia had been involved in a drinking and driving accident that had seriously injured her sister's boyfriend and killed another young man. The investigation at the detention center uncovers a lot of secrets that some of the residents would prefer to keep well hidden.
Jack and the team investigate when Sadik Marku's son goes missing along with the boy's mother, and Samantha worries that Jack is more interested in settling an old score with Marku than with finding the missing woman and boy.
The team investigates when Aaron Gibbs ends up missing one night and soon learn that he had been lying to his wife about quitting his job, and had been working nights in a fight club. During the course of the investigation, Jack and the others learn that Aaron's disappearance was connected to events that took place during Hurricane Katrina, when Aaron was fighting to save his sons, and follow the trail of evidence, believing that the events of that night in New Orleans hold the key to finding the truth about the missing man.
Martin brings the team in on the hunt for a young woman that went missing after a priest attempted to exorcise a demon from her. He begins to feel guilty when he finds out he used to work with her, but doesn't remember her.
Jack and the team investigate the disappearance of Alex Stark after his girlfriend reports him missing, and soon learn that Alex didn't own a cleaning business like he said he did but was actually involved in an illegal gambling operation. Jack goes undercover at a club that Alex would gamble at to find out what happened to him, and ends up being taken hostage by an associate of Alex's who becomes convinced that Jack is actually there to kill her. Unfortunately for Jack, his team believes that he has changed his cover story and has no idea that he's actually been kidnapped.
The team investigates the disappearance of social worker Eric Hayes, who had given thirty days notice to his job not long before. When their investigation leads them to a young pregnant woman who had already lost one child to the system, the agents begin to believe the disillusioned social worker may have been having an affair but soon discover that he may have been trying to right the wrong that drove him from his job. Danny has trouble with the investigation, as it reminds him of his own experience in foster care. Jack confides in Samantha about his relationship with Ann, but it may be too late.
When 17-year-old Ted Soros goes missing after a basketball game, the team begins an investigation, soon learning that Ted was an emancipated minor who was living on his own to attend a school with an exemplary basketball program. Learning he had recently contacted his mother with a request for legal advice from an uncle, the team begins to suspect that Ted may have done something that he could face criminal charges for, and realise that Ted's secret is connected to a university recruiting party. While the team works Ted's disappearance, Jack learns from Ann that she lost the baby, and waits for her at the clinic while she seeks medical attention.
The team tries to determine whether or not the recent disappearance of an air traffic controller has connections to the Middle East. The team soon learns that his wife died in an automobile accident and he was having an affair with her sister.
Barry Rosen goes missing shortly after being poisoned with bleach in a chili eating contest. While investigating Barry's disappearance, the team soon learns that he had been approached to throw the eating contest, and also that he had been spending a lot of time with a local prostitute in an effort to learn how to act around women. Danny is caught in the middle when Carlos asks him for a letter of reference in an upcoming custody review, and Elena informs him that Carlos is actually suing her for sole custody of Sofie. Danny warns Carlos that he is not going to be caught in the middle.
The team searches for missing water plant supervisor Jason Turner, and learn that he had become the target of a lot of anger after recent layoffs at the plant. Carlos comes to the office looking for Elena.
Elena is frantic when her daughter Sofie goes missing, and the team has a full schedule as they must also search for a missing female tourist named Jenny.
The team searches for a fifteen-year-old girl who lived with her grandfather and was last seen at an Internet café. Sam gets an unexpected visit from her estranged sister.
A former soldier, now stuntman, goes missing and the team learns that he changed his will only short time before he went missing which makes them wonder who needed the money.
The team searches for Chris Manning, a family court judge with a soft side who went missing after meeting with a young boy caught between his mother and his abusive father. Suspicion initially turns anyone Manning may have riled up due to his court rulings, but after his clerk is shot in what appears to be an attempt on Manning's life, the team learns that the secret behind Manning's disappearance is tied up with something that happened over twenty years earlier.
A high school student goes missing after leaving her prom early to get some rest in her hotel room, leaving behind a bloody dress and a lot of questions about what may have happened to her.
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