Mbeki is also known as a controversial leader of South Africa because of his stance on HIV/AIDS. He believes HIV is not directly linked to AIDS, and has publicly stated that AIDS is caused by a number of other factors, most having to do with poverty, malnutrition, other sexually transmitted infections, contaminated water, and poor living conditions. He has not fought against the misconceptions that AIDS can be caught by hugging infected children and babies.

Mbeki has appointed a circle of "AIDS dissidents," who are doctors and scientists who support him in his stance on the lack of a link between HIV and AIDS. The majority of medical health professionals and scientists across the world, however, acknowledge a link between the virus and deficiency syndrome. Last year, in the South African city of Durban where the world's biggest AIDS conference was being held, Mbeki gave a speech and disappointed many by focusing on how poverty attributed to the spread of AIDS, instead of talking about what the government could do to fight and combat HIV and AIDS.