Dr. Henry Morgan (Ioan Gruffudd) takes a seat on subway train next to a beautiful woman who is intrigued by how well he knows her simply through observation. Plans are made for a date. Then… CRASH! The subway car is involved in a horrendous accident. Many are injured. Many are dead; including the lady Henry just met. This beautiful woman has encountered her final fate. For Henry, however, this is just part of a series of “ends” in a long life that had only one beginning.
200 years ago, Henry was shot while trying to save another man on a ship during a violent storm at sea. Since that night, every time he dies, he always returns in water, and he’s always naked. There’s almost nothing in life that Henry hasn’t done—except leave it. The only person who knows his secret is his best friend, Abe (Judd Hirsch).
Detective Jo Martinez (Alana De La Garza) is called to investigate the fatal subway tragedy. She finds the old stopwatch Henry had with him during the crash. Jo is ordered by Lieutenant Joanna Reece (Lorraine Toussaint) to determine what happened to the conductor. Henry, who happens to be New York’s star medical examiner, is just beginning the autopsy with his colleague Lucas (Joel David Moore) when Jo arrives. Once again, Henry accurately deduces information about a person he’s never met. Jo is a little unsettled by this.
Henry believes the conductor was poisoned. That means Jo has 15 homicides on her hand. Henry receives a phone call from a stranger who wants to know how he survived the subway crash. The caller says he knows what he is. Henry is visibly shaken. He makes plans to get out of town fast, but Abe wants him to stay put. It won’t be easy. Henry refuses to get close to anyone. A past relationship with a woman named Abigail is to blame. Nevertheless, he opts to stay in New York. He’s not going to run.
The person who called Henry isn’t the only one who knows he was on that subway train. Jo figures this out, too. An envelope addressed to Henry from his “fan” shows up at the ME’s office. There’s a photo inside from 1955. It’s a shot of Dr. and Mrs. Henry Morgan. The woman in the picture is Abigail. In the past, she assured Henry that he was made the way he is for a reason, and it’s not for her. In the present, Henry believes the person who called him murdered the conductor to prove that he wouldn’t die. He’s being challenged to find this guy.
Henry takes some of the conductor’s blood. He asks Abe to kill him with it so he can find out what type of poison was used. The strategy works. Henry barely has time to digest the information he learns when he’s brought in to the police precinct by Jo. He lets her know that the killer was on the train. He has her walk through a hypothetical as if he were the prime suspect, which he actually is. There’s not enough evidence to hold him. Henry is free to go back to work where he continues to unravel clues on the case.
Henry and Jo follow a lead that brings them to the home of a man named Hans Koehler. They find a laboratory set up in the garage. When Koehler returns home, he throws a poisonous mixture at Jo. Henry is able to save her through quick action, but Koehler gets away. The suspect may have acted out of revenge. The conductor was operating the train that killed his wife. This has Henry questioning his own role in Koehler’s motive.
Jo joins Henry for a drink. She’s impressed and intrigued by him. Some personal details are revealed including how Jo’s husband died. She still feels a part of him inside her. Henry assures her that it will never go away. As for the investigation, Henry suspects Koehler may be planning a bigger mass murder at Grand Central Station. This is where his wife died. The race is on to find a killer in one of New York’s busiest venues.
Henry realizes Koehler is planning to release poison through the ventilation system on the roof. BANG! Jo is shot by the suspect. She fights to regain full consciousness while Henry struggles to stop Koehler. BANG! Henry is shot, too. He manages to tackle Koehler as the two of them plunge off the rooftop. CRASH! Henry’s lifeless body rests atop a shattered cab windshield.
Jo awakens inside a hospital. Henry is at her bedside. He explains that Koehler decided to take his own life. In her hazy state, Jo thought they both had gone off that rooftop. Henry quickly dismisses this notion. Then he gets a phone call. It’s the same person from before. The caller knows that Henry also plunged off the roof. He knows that he returned from the incident because death doesn’t seem to be an option for either of them. They are the same. Jo asks Henry if he’s okay. She’s truly concerned. Henry says, “I’ll survive.”
A flashback shows the day Henry first met Abigail. It's when he first met Abe, who was a baby the two of them found during World War II. They share a truly special bond. Henry knows our lives add up to a series of moments that stick with us. They mark our souls forever. He’s about to experience more of those moments with Jo, who has requested him as the ME on her latest case. Abe hands Henry his jacket so the two partners can be on their way to a new beginning.