Microserfs questions the meaning of life. Young and ambitious college graduates are exhilarated to be hired by Microsoft. They among the elite. They work ridiculously long hours, often all night and into the early hours of the morning. They work weekends. All they do is work. At first they love it. They are accomplishing great feats. They are creating tools for the coming generations. They are on top of their world.

However, the neophytes soon find that all this work is dissatisfying, even if they are making a lot of money and have job security. They have no time to relax. Most of the time they are under pressure to meet unreasonable deadlines.  But sometimes, they sit around and wait for hours, days, sometimes even weeks, for a new project. In the lag times, Dan, the protagonist, begins to wonder if he has a life beyond work; little else is going on and he frequently feels lonesome and empty.

In the end, Dan realizes that the security and the money are not enough. For him, love is much more fulfilling. This love extends to Karla, his woman friend, as well as to his parents, to whom he learns to open up. The love also extends to himself. He starts eating better, remembering that he is more than just a brain. He is a body too. He has needs that are not completely filled by creating computer programs. Life is so much more than money and producing product. Life it touching other people, both physically and emotionally.

All the originally single characters in this story find supportive relationships by the novel’s end. Dan's parents become surrogate parents for all of them.  The characters become one big happy family, full of strengths and weaknesses.

Other minor themes include issues of health and nutrition, with one section of the group surviving off snacks and two other characters at the other extreme, surviving off protein powders and vitamin supplements. There are points of health discussed. First there is Ethan's bout with cancer and then Dan's mother's stroke. There is irony in Dan's mother's case, since she had recently been exercising and seemingly getting stronger as she approaches her sixtieth birthday. She even won a swimming match.  She goes from one extreme to the other, ending up completely paralyzed from a stroke.  One thematic paradox includes a discussion about bodybuilders and taking steroids juxtaposed with a woman giving birth to a baby. When one considers the body a potentially fertile nursery for a growing fetus, one looks at the body through a different perspective. Dusty, for instance, had previously groomed her body to look good at bodybuilding events. But when she became pregnant, she is forced to look at her body as the incubator for her unborn child. Throughout her pregnancy, Dusty worries that some of her choices to be outwardly beautiful may have affected what she now knows is the most precious thing in the world:  her child.