The relationships among nutritional status, infectious disease, and the immune system suggest that nutrition may be a cofactor in human immunodeficiency virus (HIV) progression. We examined nutrition as a cofactor in HIV disease by reviewing the current literature on the interactions of nutrition, infectious disease processes, and immune system dysfunction. Studies demonstrate that poor nutritional status and infection affect the immune system and interact with each other. This relationship leads to the development of opportunistic infections and malignancies, which may result in a diagnosis of acquired immunodeficiency syndrome. Moreover, evidence from our review indicates that nutritional status may play a role in HIV disease progression. We recommend that clinical trials be conducted to evaluate general malnutrition and the efficacy of supplementation with specific nutrients at various stages of HIV disease.