Since the beginning of the acquired immune deficiency syndrome (AIDS) pandemic in 1981, research on human immunodeficiency virus (HIV) has been focused on mechanisms by which the virus escapes from immune surveillance. Several human leucocyte antigen haplotypes have been shown to be associated with rapid disease progression or resistance to disease progression. In addition, HIV is able to down-regulate major histocompatibility complex type I (MHC-I) on the surface of the host cell. For this down-regulation HIV seems to use three different mechanisms mediated by three different viral proteins. The viral Tat protein represses transcription of the MHC-I, Vpu retains nascent MHC-I chains in the endoplasmic reticulum and Nef mediates selective internalization of MHC-I molecules from the plasma membrane. The last mechanism also provides protection to natural killer cells that attack cells with little or no MHC-I on the cell surface. Together these mechanisms provide a very efficient escape from the host immune system.