Clinical and preclinical studies have found sex-specific differences in the discrimination and perception of nociceptive stimuli. This article reviews the current literature concerning the biological basis of sex differences in the behavioral response to persistent inflammatory and chronic pain stimuli. The emerging picture from both clinical and preclinical studies suggests that the basis of these differences in nociceptive responses to such stimuli resides in the regulatory activity of gonadal hormones in the central nervous system. Published reports suggest that pain management targeted at female patients should consider hormonal factors during the female reproductive cycle.