In recent years, lipodystrophy and its related complications have changed from an anecdotal issue into a major problem for HIV-infected patients on antiretroviral therapy. Despite great efforts to achieve a consensus in defining this problem, a simple, readily available definition is still lacking. More comprehensive knowledge of the underlying molecular basis and the natural history of body fat changes and metabolic abnormalities is needed to make progress. Also, an objective assessment of body fat is still to be incorporated in clinical practice, so interventions to prevent or treat body fat changes cannot be adequately monitored. Several objective techniques have been used, and all of them have limitations and advantages. There seems to be a good correlation between different techniques for measuring fat, but that is not the case for detecting fat changes. A huge amount of data have been generated on how to manage lipodystrophy. Nevertheless, there is no clinically proven treatment for any feature of lipodystrophy. The only intervention that has been shown to reverse lipoatrophy is the discontinuation of thymidine analogues, but the results obtained are partial or modest at most. Structured therapy interruptions have become an increasingly popular strategy aimed at preventing or reducing antiretroviral drug toxicity, but little objective data exist on their impact on body composition of HIV-infected patients. The issue of body composition has become extremely important for the adequate management of HIV-infected patients.