Human immunodeficiency virus type 1 (HIV) infection and antiretroviral therapy (ART) have long been associated with abnormalities in adipose tissue distribution and metabolism. More-recent evidence demonstrates that adipocytes and adipose-resident immune cells have a role in the response to HIV. Clinical and laboratory studies indicate that viral proteins and antiretroviral medications alter adipocyte biology to enhance the persistent, systemic inflammatory state characteristic of untreated and treated HIV infection. Relationships between body composition and lymphocyte populations, cellular immune activation, and immune reconstitution in HIV-infected individuals receiving ART suggest that adipose tissue may also affect cellular immune function. This is further supported by in vitro studies demonstrating the effect of adipocytes and adipokines on lymphocyte proliferation, differentiation, and activation. Synthesis of the literature on adipose tissue biology and immune function in uninfected individuals may shed light on major outstanding research questions in the HIV field.