Over the course of Millennium Approaches the characters become more and more isolated. Prior, sick with AIDS, is abandoned by his lover Louis. Harper's worst fears come true when her husband, Joe, admits that he's gay. By the end of the first part of Angels in America, her only friends are imaginary. And then there's Roy Cohn, who is also sick with AIDS. After a life of corruption, Roy is left alone on the floor with no one to talk to but the ghost of a woman he used illegal means to get executed. On the other hand, out of the wreckage of their past relationships, Joe and Louis come together. Will the relationship work? Will they escape isolation? Can these two men, who walked out on their previous relationships, be happy together?
Almost every character in the play experiences isolation in some form. By the end, though, these characters are offered comfort through new relationships, self-realizations, and supernatural occurrences.
The play suggests that relationships are temporary and loneliness is a natural human state.