Monica (Roma Downey): Monica is the main character of the show. Sweet and tender, she was promoted from the Search and Rescue department to become a caseworker, with Tess, to help people, delivering them a message of hope from God. She also has a weakness for coffee, especially mocha lattes.

Tess (Della Reese): Tess is the second protagonist of the show. She also happened to be Monica's angelic supervisor. Sometimes tough but always compassionate, she would eventually brighten everyone's spirits by singing with her melodic voice. A car and a dog were both given to her, both of which she values dearly, and an iguana, from a dying boy, which she tolerates. She is very frank and honest about the truth, and usually tells people what they have to hear, not what they want to hear.

Andrew (John Dye, 1996-2003, seasons 2-9): Andrew became an all-episode character in the third season. He is an Angel of Death, that is, one of the angels that takes people who die to their eternal fate, heaven or hell. Andrew was a caseworker before he was promoted. He still helps the other angels, esp. Monica & Tess, in their casework. He hates being stereotyped as a Grim Reaper.

Gloria (Valerie Bertinelli, 2001-2003, seasons 8-9): Gloria is an inexperienced angel, because she was created by God during one of Monica's assignments (in the seventh season). But she's highly intelligent and constantly learns new things, like human strength and weakness. She's good with technology, as well. Although initially shy, she adds a lot of humor to the show.