All steps in the HIV lifecycle--entry, assembly, budding, induction of signal transduction and subsequent cell activation--are complex multifactorial mechanisms where cholesterol and sphingolipids (glycosphingolipids--GSLs and sphingomyelins in mammalian cells) are closely involved. Here we will review the contribution of these heterogeneous membrane lipid microdomains, referred to as lipid rafts, DIGs (detergent-insoluble glycolipid-enriched complexes), DRMs (detergent-resistant membranes), GEMs (glycolipid-enriched membranes), caveolae, TIMs (Triton-insoluble membranes) for interactions of HIV with the host cell. The accurate terminology was discussed elsewhere, and to simplify matters we will use rafts or lipid rafts throughout the review.