Nutritional deficiencies are commonplace in patients with human immunodeficiency virus type 1 (HIV-1) infection, and recent research has indicated that nutritional factors may play an important role in the pathogenesis of HIV-1 disease. Although nutritional deficiencies are unlikely to be the primary causative factor in disease progression, they may contribute to cognitive dysfunction, neurologic abnormalities, mood disturbance, and immune dysregulation associated with HIV-1 infection. Furthermore, deficiencies of specific micronutrients have been associated with increased risk of HIV-1-associated mortality. This article will briefly summarize the role of macronutrient deficiency, the interactions of specific micronutrient deficiencies with neuropsychiatric functioning, and the role of these factors in HIV-1 disease progression. Since recent research has shown that normalization of many nutritional deficits and supplementation beyond normal levels are associated with improvements in neuropsychiatric functioning, potential treatment implications will also be discussed.