Sex-related influences on pain and analgesia have become a topic of tremendous scientific and clinical interest, especially in the last 10 to 15 years. Members of our research group published reviews of this literature more than a decade ago, and the intervening time period has witnessed robust growth in research regarding sex, gender, and pain. Therefore, it seems timely to revisit this literature. Abundant evidence from recent epidemiologic studies clearly demonstrates that women are at substantially greater risk for many clinical pain conditions, and there is some suggestion that postoperative and procedural pain may be more severe among women than men. Consistent with our previous reviews, current human findings regarding sex differences in experimental pain indicate greater pain sensitivity among females compared with males for most pain modalities, including more recently implemented clinically relevant pain models such as temporal summation of pain and intramuscular injection of algesic substances. The evidence regarding sex differences in laboratory measures of endogenous pain modulation is mixed, as are findings from studies using functional brain imaging to ascertain sex differences in pain-related cerebral activation. Also inconsistent are findings regarding sex differences in responses to pharmacologic and non-pharmacologic pain treatments. The article concludes with a discussion of potential biopsychosocial mechanisms that may underlie sex differences in pain, and considerations for future research are discussed.Perspective-This article reviews the recent literature regarding sex, gender, and pain. The growing body of evidence that has accumulated in the past 10 to 15 years continues to indicate substantial sex differences in clinical and experimental pain responses, and some evidence suggests that pain treatment responses may differ for women versus men.Research regarding sex and gender, differences in pain has increased substantially in recent years. As Fig 1 depicts, publications regarding sex, gender, and pain have increased at a much greater rate over the past 25 to 30 years relative to the pain field in general. In particular, a dramatic increase in publications began in the mid-1990s, which may be attributable to several influential review articles along with other events occurring in the 1990s that drew considerable attention to the topic. In 1992, an important publication by Karen Berkley 32 highlighted the importance of sex-related issues in neuroscience research. This brief paper included a survey of 100 articles in reputable neuroscience journals, which found that 45% of the articles failed to report the sex of their subjects, and the author stated "… the differences between females and males, which we all know to be important, can and should be exploited in scientific research." Shortly thereafter, an editorial appeared in The Journal of Pain, which encouraged Address reprint requests to Dr Roger B. Fillingim, University of Florida, 1329 SW 16th Street, Suite 5180, PO Box 103628...