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Publisher Summary This chapter describes the function of human immunodeficiency virus (HIV) accessory genes—vif and vpu. Primate immunodeficiency viruses, including HIV‐1, are characterized by the presence of a number of viral accessory genes that encompass vif, vpr, vpx, vpu, and nef. The vif, vpr, and nef genes are expressed in most HIV‐1, HIV‐2, and Simian immunodeficiency virus (SIV) isolates. In contrast, the vpu gene is found only in HIV‐1 and some SIV isolates. The vpx gene is not found in HIV‐1 isolates, but is common to HIV‐2 and most SIV isolates. It has been indicated that none of the primate lentiviral accessory proteins has enzymatic activity. Instead, it appears that these proteins serve primarily as adapter molecules to mediate the physical interaction of other viral and/or host factors. Several lines of evidence suggest that Vif exerts its function through interactions with species‐specific host cell factor(s). Fractionated extraction of Vif‐transfected HeLa cells reveals that Vif partitions between soluble and detergent‐insoluble fractions. Vpu mediates the efficient release of viral particles from HIV‐1‐infected cells.