PURPOSE OF REVIEW Adipose tissue pathology plays a central role in lipodystrophy. This review discusses the mechanisms by which adipose tissue responses to specific antiretroviral therapy determine clinical outcomes, and key recent data are examined that can inform the successful avoidance or management of such toxicities. RECENT FINDINGS Changes in body composition and hyperlipidaemia that occur with the use of certain thymidine analogues and protease inhibitors are accompanied by profound alterations in adipose tissue. Drug toxicity in adipocytes affects the homeostatic regulation of adipocytokines secreted from adipose tissue that mediate proinflammatory and metabolic effects, both locally and in peripheral tissue. The inflammatory component of adipose pathology may also explain slow gains in fat after switching from toxic therapies. SUMMARY Lipodystrophy can be avoided by selecting therapies with benign effects on adipose tissue. Switching from certain HIV protease inhibitors may normalize the metabolic profile fairly rapidly. For individuals living with an ongoing burden of lipoatrophy, however, reversal of pathology appears slow, and the systemic implications of adipose pathology per se as a risk factor for cardiovascular disease should be considered. Further investigation of adipose pathology for disease in the HIV community is warranted, with the potential for explorations in therapeutic intervention.