Although, overwhelmingly, behavior is similar in males and females, and, correspondingly, the brains are similar, sex differences permeate both brain and behavioral measures, and these differences have been the focus of increasing scrutiny by neuroscientists. This Review describes milestones from more than 3 decades of research in brain and behavior. This research was necessarily bound by available methodology, and we began with indirect behavioral indicators of brain function such as handedness. We proceeded to the use of neuropsychological batteries and then to structural and functional neuroimaging that provided the foundations of a cognitive neuroscience-based computerized neurocognitive battery. Sex differences were apparent and consistent in neurocognitive measures, with females performing better on memory and social cognition tasks and males on spatial processing and motor speed. Sex differences were also prominent in all major brain parameters, including higher rates of cerebral blood flow, higher percentage of gray matter tissue, and higher interhemispheric connectivity in females, compared with higher percentage of white matter and greater intrahemispheric connectivity as well as higher glucose metabolism in limbic regions in males. Many of these differences are present in childhood, but they become more prominent with adolescence, perhaps linked to puberty. Overall, they indicate complementarity between the sexes that would result in greater adaptive diversity. (C) 2016 Wiley Periodicals, Inc.