This article first presents an overview of published literature documenting the role of the scavenger receptor CD36 in activation of brain microglia with reference to brain pathologies such as Alzheimer's and malaria. Second, the possibility that CD36 may play a role in brain FA metabolism is discussed. Long-chain polyunsaturated fatty acids (PUFAs) are important for brain function and are mostly derived from the plasma. Based on its role in facilitating FA uptake in several tissues and cell types, CD36 expressed on microvascular endothelial cells in the brain may facilitate local uptake of PUFAs. Alternatively, CD36 may influence brain FA supply indirectly via impacting utilization of dietary FA or their metabolism in tissues such as the liver. We examined the possibility that CD36 expression impacts brain function by evaluating the behavior of CD36 null mice using a battery of standard tests. Our data indicate that CD36 deficient mice have normal patterns of activity, anxiety and exploration of novel environments. However they appear to have a significant impairment in learning ability. These findings could provide a new perspective regarding the regulation of brain lipid metabolism.