Abstract: Primate evolution is marked by a dramatic increase in brain size and complexity. This is especially true along the lineage leading to humans, little is known about the underlying genetic cause of this expansion. To address this problem, the evolutionary rates of a large set of genes implicated in brain development or physiology are examined in primates and other mammals. This study suggests that genes involved in brain development are evolving faster in primates than other mammalian taxa, and implicates a number of genes involved in this trend. Two of the rapidly evolving genes are known to cause primary microcephaly when mutated. Genes implicated in primary microcephaly could offer an intriguing glimpse into the genetic causes of brain size expansion in primates. Primary microcephaly is a genetic disorder that leads to a cranial capacity about 4 SD below the mean at birth. However, the general brain architecture is left intact, suggesting these genes regulate brain size alone. Therefore, genes implicated in primary microcephaly seem to be likely substrates for selection to increase brain size. Sequence data in primates suggests that selection is acting on these genes along the lineage leading to humans, though not at the same strength and not at the same evolutionary times along the lineage. For two of these genes, microcephalin and ASPM, evidence is further presented for recent selection acting on one haplogroup at these loci since human divergence from chimpanzee. The origin of this selected haplogroup at microcephalin is shown to likely arise from an admixture event with an archaic Homo lineage, such as Neanderthals. Together, these studies identify a trend of positive selection acting on genes involved in brain development, and specifically strong selection acting on genes known to regulate brain size. Furthermore, some suggestions to human population history are offered.