Abstract Evolution of the prefrontal cortex was an essential precursor to civilization. During the past decade, it became increasingly obvious that human prefrontal function is under substantial genetic control. In particular, heritability studies of frontal lobe-related neuropsychological function, electrophysiology and neuroimaging have greatly improved our insight. Moreover, the first genes that are relevant for prefrontal function such as catechol- O-methyltransferase (COMT) are currently discovered. In this review, we summarize the present knowledge on the genetics of human prefrontal function. For historical reasons, we discuss the genetics of prefrontal function within the broader concept of general cognitive ability (intelligence). Special emphasis is also given to methodological concerns that need to be addressed when conducting research on the genetics of prefrontal function in humans.