Morphological changes related to altered distribution of regional adipose tissue are well characterized as a potential complication of antiretroviral treatment regimens that can be physically disfiguring and negatively affect the quality of life. Lipoatrophy and lipohypertrophy often occur independently of one another, and the risk of developing these conditions has been associated with specific antiretroviral medications but can also be influenced by a number of host factors. This review details our current understanding of the etiologies of lipoatrophy and lipohypertrophy, including evidence from recent clinical trials, and describes strategies available to manage these conditions. The potential increase in risk of cardiovascular disease associated with these metabolic disturbances is also discussed.