As a result of the great benefit of highly active antiretroviral therapy (HAART), acquired immunodeficiency syndrome (AIDS)-related deaths have dramatically declined during the last decade. However, mortality due to non-AIDS conditions seems to be on the rise in this population. Metabolic complications are the major drivers of an increased risk of cardiovascular events, diabetes, and hepatic diseases in the human immunodeficiency virus (HIV) population. Indeed, in this setting the metabolic syndrome displays characteristic features, as well as particular pathogenic mechanisms. Therefore, early identification and management of metabolic complications taking into account the specific influence of HIV and antiretroviral drugs is warranted in this population. Management of overt lipid disorders, lipodystrophy, diabetes, and steatosis is the key to improving survival in this new generation of HIV patients.