Since the beginning of the epidemic of acquired immunodeficiency syndrome (AIDS), evidence has accumulated that genetic factors are involved in the pathogenesis of the disease. Among the candidate molecules suspected to control susceptibility to human immunodeficiency virus (HIV) infection and fast or slow progression of AIDS are the human leukocyte antigens (HLA). Investigating HLA-HIV correlation was mainly performed by investigating cohorts of patients with HIV/AIDS for a period of time and then statistically correlating certain features of AIDS with particular HLA alleles. This type of in vivo investigations resulted in the generation of an immense literature on the subject with so many HLA alleles being found to correlate with certain features of AIDS. Because of the complexity of AIDS pathogenesis and the involvement of many factors in the disease process, the different investigators failed to agree on the involvement of certain HLA molecules in AIDS pathogenesis. Some reports deny, or fail to confirm the existence of association between HLA and HIV progression to AIDS. This is probably due to the different ethnic backgrounds of the populations studied, the complexity of the HLA system, and to the ways these studies were conducted. This article briefly addresses our current knowledge on the HLA-HIV correlation in vivo and discusses alternative in vitro studies.