Variability, both at the population (interhost) as well as at the individual (intrahost) level is a key property of HIV that stems mainly from the inherent infidelity of the reverse transcriptase enzyme that the virus uses to transcribe its RNA genome into DNA so that it may be integrated into the human genetic material and propagated along with it. The lack of proofreading mechanisms, high turnover of virions, and propensity for recombination also contribute to the extensive variability of HIV. These parameters provide the virus quasispecies with an impressive capacity to adapt to immunologic, pharmacologic or other selection pressures and have important implications for the diagnosis of new infections, the monitoring of antiretroviral treatment response, and effective vaccine(s) design. Herein, we discuss in detail the global genetic variation of HIV-1 infection.