When successful veterinarian Dr. George Coleman learns that his ex-girlfriend Dorothy Crane has inherited the hospital where he works and is now his boss, he is less than thrilled. George, who would rather spend time with his animal patients than with their human owners, is a stark contrast to the cheerful and optimistic Dorothy, who immediately inserts herself into the hospital business. As the sparks fly between George and Dorothy, the rest of the staff members struggle to maintain composure and do their jobs, including Dr. Doug Jackson, Dr. Yamamoto, Juanita, Nurse Angela and last but not least, "Dr. Rizzo," the resident capuchin monkey at Crane Animal Hospital and George's closest companion.

When Doug's dog "Little Miss Can't Be Wrong," gets injured and needs surgery, he enlists George to perform the operation when he realizes he's too nervous to do it himself. Dorothy steps up her efforts to be accepted by the staff when she finds out they've been doing Happy Hour without her. Meanwhile, Angela decides to try and sell Dr. Rizzo's artwork to a gallery but Dr. Rizzo is not so keen on the idea.

When a young boy's busy father leaves him at the hospital with their Parson Russell Terrier in kidney failure, George must tap his softer side to help the boy deal with the situation. While Dorothy tries to give the case to Doug, who is brilliant with kids, George insists that he is up for the challenge.

Dr. Yamamoto performs a successful emergency surgery on the Mayor's dog and becomes a media darling, much to George's dismay. Meanwhile, Dorothy, hires an accomplished new doctor at the hospital, Dr. Jill Leiter, who is beautiful, tough, and sure to keep George on his toes.

When George's overbearing mother Virginia shows up at the hospital with her sick cat, named "cat," George must heal the cat or risk the alternative - having to keep her company to fill the void. Meanwhile, Dorothy counsels Dr. Leiter who must face the board of directors before she can settle in at the hospital.

George begins to feel threatened with Jill's strong new presence at the hospital. Annoyed by this increasing competition, George attempts to sabotage one of Jill's operations. Meanwhile, Dorothy takes on judging Crane Animal Hospital's Halloween pet costume contest and struggles with the temptation to take a bribe.

George begins treating a cockatoo that keeps mysteriously ingesting chocolate. While George tries to manage the eccentric owner, Sabrina French, Doug sets his sights on the socialite granddaughter, Tinsley French. Dorothy begins a movie night but when only Yamamoto shows up the two make the most of it. Meanwhile, Angela and Dr. Rizzo have to call the cable guy when their favorite legal program "Law of the Jungle", is interrupted. Smitten with the cable guy's take-charge manner, Angela schemes to get him back ASAP.

Dr. George Coleman and Dorothy Crane disagree on how best to deal with an overweight dog, "Ralphie", and the over-indulging owner who is over-feeding him. George prefers threats and humiliation while Dorothy prefers a gentler approach. Meanwhile, Dorothy establishes a weekly "snack & chat", which conflicts with the guys' poker night.

When George's Mother invites him to Thanksgiving Dinner, George forces Doug and Doug's dad to join them only to discover there might be sparks between George's Mom and Doug's Dad. Meanwhile, Dorothy spends Thanksgiving with Juanita's family and Angela sets out to distract Yamamoto from calling his wife.