Efforts to understand the biological substrates of sex differences in cognition require examination of brain anatomy (structure) and physiology (function). Technological and methodological advances have increasingly enabled the examination in humans of the neurobiology of behavior across the lifespan. Starting in the early 1980s, a genre of safe methods for obtaining reliable measures of brain structure and function have become available. While most applications of these methods have been in people with different brain disorders, several sufficiently large-scale efforts have included healthy people and have examined sex differences in brain anatomy and physiology. Fewer studies have related such measures to cognitive performance; nonetheless, there is considerable convergence of replicated findings to support at least some hypotheses worthy of further refinement. This article will briefly describe the main findings from neuroimaging applications in which sex differences were established. These findings substantiate some hypotheses on neural substrates for sex differences in cognition.