Sex differences have been reported in the experience of pain and in the prevalence of chronic pain conditions. However, recently work has uncovered biological differences in the utilization of immune cells and basic function of afferents that shed light on the underpinnings of these sex-dependent findings. In addition, work in healthy controls and chronic pain patients have highlighted biases in attribution of pain and assessment of pain intensity that further reinforce sex differences. Together, the combination of biological differences, distinct psychological coping strategies and outside bias result in the maintenance of disparities in the experience of pain based on sex. Recognition of sex differences and the underlying mechanisms can only improve treatment and patient outcomes.