Lipodystrophy, and the metabolic alterations (dislipemia, insulin-resistance) associated with human immunodeficiency virus (HIV) infection, is a multifactorial syndrome due to the interaction of host related factors (cellular immune status, diet, gene mutations), viral factors (cytokine synthesis, polyunsaturated fatty acid or PUFA depletion), and pharmacological effects (mitochondrial DNA-polymerase inhibition, lipolysis inhibition, adiponectin synthesis reduction). HIV probably modifies the adipocyte differentiation and the lipid metabolism. This retroviral effect is mediated by proinflammatory cytokines (tumor necrosis factor) and the participation of other factors (drugs, diet), all in the context of a particular host genetic setting. The adipocyte (and several cellular receptors, fatty acids, membrane proteins, and cytokines) plays a central role in the pathogenesis of HIV-associated lipodystrophy.