Women are more likely than men to develop rheumatoid arthritis (RA), and recent data suggest that they also suffer greater disability than men with this disease. The reasons for these sexually dimorphic patterns of disease incidence and progression are unknown, but investigations into the underlying mechanisms could provide useful insights into RA pathogenesis and may also suggest new treatment approaches. The processes of sexual differentiation involve genetic input, gonadal hormone signaling and responses from target cells and tissues. Layered upon these processes are behavioral characteristics of males and females acquired as a result of their social context. Differences in disease presentation between the sexes could be the result of complex combinations of all these factors. Recent research suggests that the developmental processes of sexual differentiation might render women more susceptible than men to similar levels of immune or inflammatory burden by virtue of sex-specific differences in body composition and structure.