Weight loss and muscle wasting remain significant clinical problems, even in the era of potent antiretroviral therapy. In patients infected with human immunodeficiency virus (HIV), wasting, particularly loss of metabolically active lean tissue, has been associated with increased mortality, accelerated disease progression, loss of muscle protein mass, and impairment of strength and functional status. Factors that may contribute to wasting include inadequate intake, malabsorptive disorders, metabolic alterations, hypogonadism, and excessive cytokine production. Evidence now demonstrates that nutritional counseling and support, appetite stimulants, progressive resistance training, and anabolic hormones can reverse weight loss and increase lean body mass in HIV-infected patients. Despite a growing body of evidence on the importance of nutritional intervention to prevent wasting in adults, maintain growth velocity in children, and promote restoration of weight and lean body mass in stable, low-weight patients, no therapeutic guidelines currently exist for the management of weight loss and wasting in HIV-infected patients. Principles and guidelines for assessment and management of weight loss and wasting in patients with HIV/AIDS are presented.