Advances in the supportive care of cancer patients have led to improved long-term outcomes. Infection, however, remains the most significant complication of cancer therapy. The author reviews the impact of new cancer therapies on the risk factors for infectious complications and the impact of therapy on the alterations in host defense. The relative importance of therapy-induced changes are contrasted with immunologic abnormalities associated with specific cancers. In addition, the author contrasts these changes with the infectious complications of human immunodeficiency virus infection, highlighting common themes in immunocompromised patients.