The article reviews the evolving knowledge of sex differences in brain structure, function, and chemistry, using imaging methodologies such as fMRI, PET, SPECT, and MRI. The authors highlight that while there are many similarities between the brains of healthy men and women, there are also significant differences. Overall brain volume is greater in men, but when controlling for total volume, women have a higher percentage of gray matter, and men have a higher percentage of white matter. Global cerebral blood flow is higher in women than in men. Sex-specific differences in dopaminergic, serotonergic, and GABAergic markers indicate that male and female brains are neurochemically distinct. These differences in brain structure, function, and chemistry likely impact normal and abnormal behavior and may influence the prevalence and course of neuropsychiatric disorders. The authors emphasize the need for more hypothesis-driven research to evaluate sex differences in the living human brain and to collect information about menstrual cycle status and phase to better understand the effects of sex on brain function.The article reviews the evolving knowledge of sex differences in brain structure, function, and chemistry, using imaging methodologies such as fMRI, PET, SPECT, and MRI. The authors highlight that while there are many similarities between the brains of healthy men and women, there are also significant differences. Overall brain volume is greater in men, but when controlling for total volume, women have a higher percentage of gray matter, and men have a higher percentage of white matter. Global cerebral blood flow is higher in women than in men. Sex-specific differences in dopaminergic, serotonergic, and GABAergic markers indicate that male and female brains are neurochemically distinct. These differences in brain structure, function, and chemistry likely impact normal and abnormal behavior and may influence the prevalence and course of neuropsychiatric disorders. The authors emphasize the need for more hypothesis-driven research to evaluate sex differences in the living human brain and to collect information about menstrual cycle status and phase to better understand the effects of sex on brain function.