Endocytosis is essential for the entry of many viruses into cells. The primate lentiviruses [human immunodeficiency virus (HIV) 1 and 2, and the simian immunodeficiency viruses (SIVs)], however, use endocytosis in other aspects of their life cycles. Here, the authors describe the ways in which the endocytic pathway is used by HIV and SIV and discuss the mechanisms through which endocytosis may contribute to the pathogenic properties of these viruses.