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As our environment becomes ever increasingly complex, understanding how sex differences impact disease risk and resilience will only become more critical. The 2019 Neuropsychopharmacology Reviews, "Sex Matters," edited by Dr. Tracy L. Bale, highlights the causal and mechanistic value in cases where significant sex differences are found, as well as when they’re not; where sex differences may arise at one period of life and disappear in another. Additionally, this special issue reinforces the message that males are not the control, and females are not more variable. The value is in appreciating the difference. Sex matters.