Painful physical symptoms are common elements within mood disorders and provide a therapeutic challenge when such patients attribute their pain to causes other than the mood disorder. These somatic presentations may lead to under-diagnosis and inappropriate treatment of patients with mood disorders. Antidepressant agents that inhibit both serotonin and norepinephrine reuptake effectively remit mood disorders, thereby providing relief of painful physical symptoms often associated with these disorders. They may also provide analgesia for neuropathic pain, such as that caused by diabetic neuropathy, which are associated with mood disorders. Newer generation dual acting antidepressants such as duloxetine and venlafaxine offer a well-tolerated and safe alternative to tricyclics. Concurrent with medication and management, the physician must educate the patient about the nature of both depressed mood and painful physical states that are augmented by and inherent in the depressive disorders. This mini review addresses the problems inherent to the treatment of painful physical symptoms in depression.