Malaria and HIV infection are both prevalent in the areas of the world where these diseases have the largest burden. Both diseases interact with one another and this interaction is especially important in areas with non-continuous malaria transmission, in pregnant women, and in patients with more severe immunodeficiency. Malaria has been implicated in transitory higher viral load and in low CD4 counts, so it could have an influence on higher transmission rates of HIV and perhaps in the course of HIV infection. Infection with HIV has been shown to cause more clinical malaria and higher parasitemia in patients living in perennial transmission areas, and higher rates of severe malaria episodes and mortality in areas where malaria is transmitted with seasonal frequency. The HIV-infected patients have also higher rates of malaria treatment failures. Co-trimoxazole prophylaxis has been shown to be effective in the prevention of some opportunistic infections in HIV-infected patients, but also in prevention of malaria episodes. Antiretroviral protease inhibitors demonstrate antimalarial effects that could have important clinical and therapeutic implications. For all of these reasons, HIV and malaria should be considered together as part of healthcare programs for both diseases in countries where their co-presence favors an interaction with important clinical consequences.