Faced with a patient who presents with unexplained disproportionate pain, a surgeon may be tempted to diagnose a low pain threshold, malingering, poor coping, anxiety, or other emotional condition. However, a variety of conditions must be ruled out before the orthopedist can prescribe watchful waiting. Computed tomography and magnetic resonance imaging can detect occult fractures, acute spinal conditions or vascular occlusions, but early on are inadequate to diagnose a compartment syndrome, necrotizing fasciitis, or reflex sympathetic dystrophy (RSD). These diagnoses underpin a pain-out-of-proportion situation whereby the patient presents with disproportionate pain following a sometimes minor trauma with normal imaging studies and otherwise nonspecific presentations. Though these conditions are well described in the literature, investigations of malpractice data reveal a non-negligible prevalence of missed diagnoses for each of these entities. Determining that a patient exhibits otherwise unexplained pain-out-of-proportion situation is the first step in making a timely diagnosis.