HIV associated lipodystrophy: abnormal central fat accumulation (lipohypertrophy) and localized loss of fat tissue (lipoatrophy). Some patients have only lipohypertrophy or only lipoatrophy; others have a mixed clinical presentation. Lipohypertrophy and lipoatrophy are distinct entities with different risk factors and underlying metabolic processes. Lipohypertrophy: enlarged dorsocervical fat pad; circumferential expansion of neck; breast enlargement (including gynecomastia); abdominal visceral fat accumulation and other new fat accumulations that are circumscribed (e.g., lipomas) or general. Lipoatrophy: peripheral fat wasting; loss of subcutaneous tissue in face, arms, legs, buttocks; involvement of face is most common. Additional features: hyperlipidemia; insulin resistance; hyperinsulinemia; hyperglycemia; low levels of high density lipoprotein; and increased risk of diabetes mellitus and atherosclerosis. Mechanisms for development are not completely understood. HIV-1 protease inhibitor drugs and nucleoside reverse transcriptase inhibitors are implicated as follows: decreased production of retinoic acid and triglyceride uptake; inhibition of mitochondrial DNA (mtDNA) polymerase gamma; inhibition of lipid metabolism; and prevention of development of adipocytes. Evidence suggests decreased insulin sensitivity, beta-cell dysfunction, and down-regulated estrogen receptor expression in adipose tissue. In absence of HAART, HIV-1 may itself cause dyslipidemia and lipodystrophy by various mechanisms. Resting energy expenditure and lipid oxidation are higher in HAART-treated HIV-positive patients with vs. without lipodystrophy.