Despite a lack of formal evidence for the efficacy of antidepressants in the treatment of CPP, several lines of evidence suggest that they may play an increasingly important role in the treatment of this disorder. Although best combined as part of a multimodal treatment package that includes psychotherapy, behavior change, and physical activation, they appear to have promise for at least a subgroup of women with chronic pain. The relative safety of these medications and the high prevalence of major depression in this population of patients make the routine empirical trial of these medications a desirable, cost- and time-effective strategy in the treatment of this disorder.