Viruses are intracellular pathogens that are subject to intense selective pressures during their ongoing battles within the host. To propagate successfully, they must exploit numerous machineries of the infected cell. Thus, studies of their replicative cycles have yielded fundamental insights into eukaryotic biology. A prime example is the human immunodefi ciency virus (HIV), which is a lentivirus that causes the acquired immunodefi ciency syndrome (AIDS). Unlike simpler oncoviruses that rely exclusively on host cell machinery, lentiviruses code for additional accessory and regulatory proteins that act as molecular switches at different stages of viral entry and exit from the infected cell. Studying the actions of these viral proteins has yielded understanding of diverse cellular functions such as the innate immunity against retroviruses, control of transcriptional elongation, export of macromolecules from the nucleus to the cytoplasm, and intracellular traffi cking of proteins (reviewed in [1])