Holly Sykes is a child when she first hears voices. She's soon comforted by an Anchorite who introduces herself as Miss Constantine. Holly is soon afraid of Miss Constantine and tells her mother about her fears. When Holly's mother, Kath, seeks help, she finds a psychiatrist named Dr. Marinus, who immediately puts an end to Holly's connection with Miss Constantine. What Kath and Holly don't know is that Marinus is really a Horologist who has been reincarnated over several lifetimes and is part of the ultimate battle of good-versus-evil against the Anchorites.

The Anchorites befriend children who are gifted with various psychic abilities. They convince the children to go willingly with them to a Chapel where the Anchorites literally feed on the children in order to keep themselves young. Through this process, they are immortal. Miss Constantine had been grooming Holly for that role and it's only Marinus' intervention that saves her.

Holly becomes a teenager and has a fight with her mother over Holly's involvement with a boy. Holly, believing she is in love and in the right, runs away from home. Her younger brother, Jacko, disappears the following day and everyone assumes that he's run away in search of Holly. Holly is devastated, believing it's her fault that Jacko disappears.

As an adult, Holly encounters Marinus again, this time in a different body, and discovers that her brother Jacko had died of a childhood illness. From that time, his body was held by a Horologist named Xi Lo. It was actually Xi Lo who disappeared and Holly is recruited to join the Horologists in what will be their final battle against the Anchorites. Holly learns that there have been dozens of victims of the Anchorites over the years and that there is a slim chance that Xi Lo – known to Holly as Jacko – might be saved in the process.

Although she wasn't aware of it, Holly has served as a host to another Horologist, Esther Little, who encountered the teenaged Holly when she was running away from home. Esther sees future events and leaves clues for Marinus that help him reweave Esther's memories into a full version of herself, though Esther is functioning without a body during the final battle against the Anchorites.

The Horologists make their way into the Chapel and the battle begins. There are casualties on both sides and it appears the Horologists will lose, but a last-minute effort by Holly saves Marinus. She literally strikes Miss Constantine in the head with a rolling pin, making it possible for her to escape. Marinus manages to get away with the help of an Anchorite who cares deeply for Holly.

Decades pass. Holly makes a life for herself and her daughter Aoife. Aoife and her husband, who is from Iceland, are killed in a plane crash along with many others during a “Gigastorm,” leaving Holly to raise her granddaughter, Lorelei. Holly eventually adopts a young refugee, Rafiq, who has diabetes. As their part of the country faces looting and a total breakdown of government, Holly fears for her adopted children more than for herself.

Just as her fears hit a peak, a huge ship arrives. Rafiq is fishing and someone from the ship asks for Holly and Lorelei by name. Rafiq is afraid but Holly soon discovers that Marinus is in yet another body, this time as a vital adviser to the Icelandic government. Marinus has located Holly and, using his Horologist abilities, manages to convince the government that Lorelei is vital to their country's well-being. Iceland, being one of the few remaining functional countries with electricity, oil, medicines, and technology, has the insulin necessary for Rafiq's survival.

Holly, knowing that her life is nearing its end, knows the best chance of survival for Rafiq and Lorelei are to go with Marinus. They part with many tears and with Holly's profound thanks to Marinus for this final act of care toward her family.