Adams was originally Smith's choice for the role of Bethany, but in order to get the movie made, he had to make some consessions, and one of them was that Adams wouldn't play the lead role. Adams was later set to play Serendipity, but Harvey Weinstein told her it probably wasn't a good idea for her to be in the film since she and Kevin Smith has just broken up.

Gillian Anderson turned down the role of Bethany Sloane. Linda Fiorentino took the part.

Brooks read for the role of Cardinal Glick after George Carlin originally turned down the role due to scheduling conflicts. Carlin later accepted the role.

Shannen Doherty was reportedly pursuing the role of Bethany Sloane.

Holly Hunter was the first choice to play God.

Jason Lee was set to play the part of Loki in Dogma but dropped back to a smaller role due to scheduling conflicts.

Alanis Morissette was originally going to play the lead role of Bethany. She got all busy with a world tour instead.

Along with Adam Sandler, he was briefly considered for the role of the demon Azrael.

Rodriguez was asked by Kevin Smith to direct the film, but, Rodriguez deemed the script too "personal" and recommended Smith direct it himself.

Adam Sandler was considered for the role of Azrael.

Dropped out because she wanted to stay in the UK and work on starting a family.