Retrovirus variation has important implications not only on virus diversity and evolution, but also on virulence, pathogenesis and the ability to develop effective antiviral drugs and vaccines. This point is easily made when one considers human immunodeficiency virus type 1 (HIV-1) and the AIDS pandemic. The high variability of retroviruses (and of RNA viruses) has its basis in the lack of elaborate proofreading and repair mechanisms during some (or all) of the steps in replication of the virus genome. In this review, I will discuss some highlights in the literature that have helped shape our understanding of retrovirus variation.