The show revolved around a group of nurses working at the same hospital as Empty Nest's Dr. Harry Weston. Initially, the main characters were strong-willed nurse Annie Roland (Arnetia Walker), sarcastic nurse Sandy Miller (Stephanie Hodge), dim-witted nurse Julie Milbury (Mary Jo Keenen) and Latina nurse Gina Cuevas (Ada Maris) who frequently reminisced about her homeland, the fictional San Peqeuno. Also in the cast were arrogant Dr. Hank Kaplan (Kip Gilman), wise-cracking orderly Paco Ortiz (Carlos Lacamara) and flaky nurse Greg Vincent (Jeff Altman). In addition, Florence Stanley had a recurring role during the first season as Dr. Riskin.
Changes were made, however, after the first season. In an effort to boost ratings, David Rasche joined the cast in the second season as Jack Trenton, a slimy white-collar criminal forced to perform community service at the hospital, and in the final season Loni Anderson joined the cast as new hospital administrator Casey McAfee. Other changes included the addition of Markus Flanagan as Luke Fitzgerald for the second season only, the dropping of the theme song altogether, having nurse Gina and Dr. Hank Kaplan get married (Gina being pregnant with Dr. Hank's child) and, oddly, having nurse Gina's extremely thick Spanish accent competely disappear. Nurse Greg Vincent was also written off after season one. In the show's final season, nurse Sandy was gone, and the show's focus moved increasingly from the nurses to the antics of Jack Trenton and his sidekick Paco the orderly.
The second season saw changes in the credits. The show's title display remained the same, but the animated outlines of the cast members were eliminated and the theme song was changed to an upbeat instrumental with a bouncy Latin beat. The third season for the most part saw a truncated opening sequence with yet another instrumental melody, dominated by flutes and piano. The Nurses title logo, still set against white, was now in a bold variation of Arial font and had a small lowercase display of the title appear (in white) along a giant, capitalized version of the name (in purple). Many episodes just featured the title briefly as a "cold open," and the cast and principal crew members were credited during the first scene of the show. When a traditional, full version of the sequence aired, black-and-white video insets of each cast member appeared against the white, while the actors names (in thin Arial) floated into place below them.