Pain has become an increasingly recognized symptom that plays a major role in the treatment of many podiatric patients. Management of this now accepted fifth vital sign can be accomplished through many avenues. Nonsteroidal anti-inflammatory medications and short- and long-acting opioids are typically used by many podiatric physicians; however, the benefits and potential hazards of other pharmaceutic approaches using antidepressants, anticonvulsants, topical medications, and other centrally acting medications must also be recognized. In addition, the role of the psychiatrist or therapist should not be neglected because many types of cognitive therapies are available to aid in treating these patients.