Men and women are different in response to experimental painful stimulation, in pain attitude such as reporting pain and pain coping behavior, in symptoms and signs of painful disorders and in response to pain treatment. Both acute and chronic pain conditions have diverse prevalence among the sexes. Overall, women have more than twice higher prevalence in painful disorders compared to men. Here I review putative mechanisms underlying sex differences in pain, including genetic factors that have sex-specific or sex-biased effects controlling pain and analgesia.