Malaria and HIV are the most important infections in subSaharan Africa, in terms of the morbidity and mortality they cause. Current data suggest a possible interaction between the two diseases. Cellular immunodeficiency due to HIV infection might increase the frequency and severity of malaria, as local populations in endemic areas become less resistant. Likewise, the onset and repetition of malaria episodes might activate HIV replication and thus decrease the number of CD4 lymphocytes and accelerate the disease course. Despite their geographical coincidence, the epidemiological profiles of malaria and HIV differ considerably. The entanglement of these two diseases has epidemiological, clinical and therapeutic consequences in subSaharan Africa that raise concerns that HIV with malaria, as with tuberculosis, is a match made in Hell.