There have been several recent reports describing gynecomastia in HIV-1-seropositive patients treated with HAART. However, the etiology of gynecomastia in this setting is far from clear. In this article, we describe the main issues in diagnosis and treatment of gynecomastia and stress the importance of differentiating between "true" gynecomastia and "lipomastia" (pseudogynecomastia), characterized by subcutaneous fat deposition. The importance of switching antiretroviral drugs is also discussed. In addition, newer medical therapies are highlighted.