David is a thirty-three-year-old orthopedic surgeon who grew up in poverty in a West Virginia coal-mining town. Haunted by the childhood death of his sister, June, who had Down's Syndrome, he strives to control his environment through medicine and photography. During the delivery of his twins, he makes a unilateral decision to send his daughter away, a choice that dictates the rest of his life. He struggles to communicate emotionally, frequently retreating into his work and his darkroom.

Caroline is an efficient, quiet nurse who harbors a secret affection for her employer, David. When he instructs her to take his newborn daughter to an institution, she visits the facility, decides it is unfit, and impulsively chooses to raise the child herself. Moving to Pittsburgh, she advocates for children with disabilities, completely transforming from a timid assistant into a fiercely protective mother.

Norah is David's younger wife, raised to follow the rules and maintain perfect appearances. Believing her daughter died at birth, she suffers from severe grief and depression, which she attempts to self-medicate with alcohol. She feels trapped in the role of a traditional 1960s housewife, eventually taking a job at a travel agency to carve out a sense of independence.

Paul is the son of David and Norah, growing up in a household thick with unspoken tension. Highly attuned to his parents' unhappiness, he often feels responsible for keeping the peace. He eventually discovers a deep passion for the guitar, using music to escape his father's rigid expectations and his mother's erratic behavior.

Phoebe is Paul's twin sister, raised in Pittsburgh by Caroline. She is highly expressive, emotional, and deeply attuned to the feelings of those around her. Unburdened by the secrecy that plagues her biological family, she lives a relatively happy life, eventually developing a love for music and a desire to marry her boyfriend.

Bree is Norah's younger sister, characterized by her rebellious spirit and involvement in the free-love movement. After a brief early marriage ends poorly, she attends college and frequently challenges traditional social expectations. She operates as a direct contrast to Norah's strict adherence to appearances, offering blunt criticism and unwavering loyalty.

Al is an observant, goodhearted truck driver who crosses paths with Caroline during a snowstorm. He slowly integrates himself into her life, bringing a steady, calming presence to her highly anxious routine. He values mobility and travel but demonstrates consistent devotion to Caroline and her child.

June is David's younger sister who died of a weak heart related to Down's Syndrome when David was a teenager. Though she passes away before the events of the novel, her early death deeply traumatizes David, motivating his actions in the delivery room.

Leo is a brilliant but senile elderly man living in Pittsburgh. He is known for his difficult, curmudgeonly behavior and paranoia, having driven away several previous nurses before Caroline takes the job.

Doro is a wealthy woman in Pittsburgh who requires a companion for her father. After her fiancé's tragic death years prior, she leads a quiet life until Caroline arrives. She eventually becomes a benefactor and close friend to Caroline, providing her with housing and support.

Sandra is a proactive mother involved in the Upside Down Society. She befriends Caroline early on, sharing her knowledge about developmental milestones and helping Caroline navigate the educational system.

Tim is Sandra's son, who also has Down's Syndrome. He frequently plays with Phoebe during their childhood and attends the same educational groups.

Kay is Norah's wealthy, put-together acquaintance. She lives a life largely untouched by tragedy, making Norah intensely envious of her ease and social grace.

Mark is Bree's boyfriend during her college years. He is a Vietnam War veteran who lost part of his foot, sharing an intense conversation with David about their similar West Virginian roots.

Howard is a stranger the Henry family meets while on vacation. He strikes up a conversation about photography with David but directs blatant, flirtatious attention toward Norah.

Duke is Paul's teenage friend who introduces him to marijuana and a less supervised lifestyle. Unlike Paul, Duke comes from a lower-income background but has highly involved parents.

Rosemary is a pregnant sixteen-year-old runaway squatting in David's childhood home. She makes elaborate paper cutouts to pass the time. David allows her to live in a duplex he buys, providing her with stability as she raises her child.

Jack is Rosemary's young son. He brings a sense of youth and energy to the duplex, allowing David a second chance to engage with a child's development.

Robert is Phoebe's boyfriend. He has a cheerful disposition and frequently speaks about his desire to marry Phoebe and buy a house, much to Caroline's anxiety.

Frederic is a businessman Norah meets during her travels. He represents a completely new chapter for Norah, far removed from the tensions of her marriage in America.

Michelle is a musician and Paul's girlfriend during his time studying in France. She is highly focused on her career and resists Paul's traditional views on marriage.

Sam is an investment analyst who engages in an affair with Norah. He attempts to maintain their connection, but Norah eventually ends the relationship.

Trace is Doro's lover. He accompanies her on social visits and plans to take her on an extended cruise.

Stuart is a respiratory therapist who has harbored feelings for Rosemary for years. He eventually offers her a stable family life.