For the effective treatment of HIV infection, combinations of antiretroviral drugs that, at various points of attack, prevent viral replication are used. After the introduction of HIV-1 specific protease inhibitors, various metabolic complications and changes in body habitus manifesting as abnormal fat distribution were observed in HIV patients. These side effects, initially assigned class-specifically to the protease inhibitors, have, however, also been frequently seen under other drug combinations. Changes to body habitus as a result of fat redistribution have mostly been designated as lipodystrophy syndrome, but are now increasingly being recognized as highly heterogeneous abnormalities. Furthermore, the disturbances of glucose and fat metabolism may occur completely independently of phenotypic habitus changes. The result is that both the suspected pathophysiological relationships and the therapeutic consequences are becoming even more complex. This paper summarizes the current state of investigations into the side effects of antiretroviral therapy and their clinical consequences.