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Melina Kanakaredes as Dr. Sydney "Syd" Hansen – A high-profile plastic surgeon who returns home for her sister's wedding. Unfortunately, her mother dies before the ceremony begins. Syd returns to Los Angeles, only to find her boyfriend cheating on her with a man. She ultimately decides to move back home to Providence to help her family, and she takes a job at a free clinic that she later ends up running. While struggling with her new specialty of family medicine while helping her family, she tries to rebuild her love life, without much luck until season 5.
Paula Cale as Joan "Joanie" Hansen – Sydney's younger sister and single mother of young Hannah. Her mother's death interrupts her wedding and, after giving birth to Hannah, she decides not to marry Hannah's father, Richie. An optimistic woman, Joanie assists her father in his practice until she discovers that her cooking, while unpalatable for humans, is a delicacy for dogs, and she opens a delicatessen bakery for dogs. Her love life, however, is as complicated as her older sister's. Though loyal to her family, Joanie often feels overshadowed by Syd's accomplishments, and they quibble frequently. Joanie senses that her parents, especially her father, tend to favor Syd, so she decides to take over as her father's caregiver after he survives a near-fatal gunshot head wound that was intended for his dog, Fearless. Joanie often makes Syd feel guilty about having her own life and priorities, but as she later learns, it stems from extreme envy. While Joanie admires her sister, she finds herself resenting her sister's sense of freedom.
Seth Peterson as Robert "Robbie" Hansen – Sydney and Joanie's younger brother. A charming bad boy who manages a pub and is a gambling addict. After much trouble, he finally settles down when he marries Tina, a divorced mother of one, Pete, and later has a son with her, Nicholas "Nick" Hansen.
Concetta Tomei as Lynda Hansen – Sydney, Joanie, and Robbie's overbearing mother. She dies before her pregnant daughter's wedding service, and afterwards appears only to Syd in dreams, giving her (often unsolicited) advice.
Leslie Silva as Dr. Helen Reynolds (season 1; guest season 2) – Sydney's friend and the original head of the free clinic. Afterwards, she returns to her hometown, leaving the clinic in Sydney's hands.
Mike Farrell as Dr. Jim Hansen – Sydney, Joanie, and Robbie's father, a warmhearted veterinarian who runs a clinic in his basement and who occasionally relates better to animals than to people.
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