Plasmodium falciparum and human immunodeficiency virus type 1 (HIV-1) infections are common in children living in sub-Saharan Africa (SSA). Both of these pathogens affect the central nervous system (CNS). Most HIV-1 infection of children in this region is acquired from infected mothers, particularly during breast-feeding and at the time of delivery. Over a third of children infected by birth will have died before their first birthday, before overt CNS manifestations have developed. The most common manifestations of primary CNS infection include neurodevelopmental delay, impaired brain growth, motor deficits, and behavioral problems. These deficits may also result from infections, neoplasm, or stroke. Cognitive impairments become more evident if the child survives for longer, but in Africa, children rarely survive past their fifth birthday. In malaria endemic areas, severe falciparum malaria usually develops after 6 months of age, and most of the CNS manifestations are more common in children over 1 year old. About 11% of children develop neurological deficits following cerebral malaria, most of which improve within 2 years of the insult. However, up to 24% of children may have neurocognitive impairments following severe malaria. The effect of milder malaria and coincidental parasitization on cognitive function is unknown. Other comorbidities that are common in SSA, such as malnutrition or micronutrient deficiencies, may influence children's neurodevelopment. The coinfection of malaria and HIV-1 may aggravate the neurodevelopmental impairments documented in these children. However, to date there are little published data, although it may have a profound effect of children living in SSA.