High genetic diversity of HIV-1 is the main factor behind the fact that HIV infection is widespread and difficult to treat. Although a limited number (or only one) of virus particles enters the blood upon infection, the particles are replicated in infected cells and rapidly produce new genetic variants that are resistant to the host immune system and antiretroviral drugs. This circumstance hampers the development of anti-HIV-1 vaccines and requires new antiretroviral drugs to be designed. The cause of the high variation of HIV-1 is related to the properties of its reverse transcriptase, which is error prone and often makes mistakes when transcribing virus RNA. Moreover, host APOBEC3-family proteins deaminate cytosines in the resulting minus strand DNA copy, leading to C/G-T/A transitions. The review considers several mechanisms that generate HIV-1 variants, including multiple recombination events between two different RNA copies colocated within one capsid. To understand the mechanisms of high genetic diversity of HIV-1 is essential for designing basically new approaches to treatment of HIV infection and AIDS.