The program is set in the (ficticious) Springton General Hospital, in a still-unnamed city (though exterior shots of Santa Christina) are sometimes used. The show centres around the lives of the hospital's staff. Almost every scene is set in the hospital or its environs - location shooting is very rare.
- Dr. Harold 'Hal' Sorenson (Ken Hunt) is the show's star and central character, and the only member of the cast to have been present for the entirety of the show's run. Initially a new resident trauma surgeon, Dr. Sorenson has 'risen through the ranks' of the hospital's staff in the last twenty years, and is now the hospital's Chief of Staff. A morose, laconic sort with no sense of humour, Dr. Sorenson has become more of an observer of events at the hospital rather than a participant.
- Dr. Sam Lenahan (Daniel Boothe) was the first Chief Surgeon at the hospital, remaining on the show from 1983 to 1987, when he was replaced by Dr. Sweeney. Dr. Lenahan was a veteran of the Korean war and an 'old warhorse' who had seen everything and was surprised by nothing.
- Dr. Violet Chalmers (Helen Campbell) began the show as Sorenson's fellow resident and sometime paramour. In 1990, Dr. Chalmers was written out of the show after Campbell's arrest and imprisonment on drug charges. She was not replaced in the true sense of the word, and other characters took over much of her role.
- Nurse Annie Gore (Rebecca Marx) joined the cast of the show in 1995 and has remained for the past eleven years. Nurse Gore is the main antagonist in the show, and serves as the 'villain' much of the time, plotting against Dr. Sorenson in a power struggle for control of the hospital's staff.