ABSTRACT Background Medical comorbidities are common among patients with temporomandibular disorders (TMDs). The authors examined the relationship between the medical comorbidities in patients with TMDs and their psychological functioning. Methods The sample consisted of 1,060 adults with TMDs, of whom 85 percent (n = 901) were female. At the time patients were evaluated at a university orofacial pain center, from 1997 through 2007, they completed medical history and psychological questionnaires. On the basis of retrospective chart reviews, the authors assessed the relationship between medical comorbidities and psychological functioning, controlling for pain severity, by using multivariate analyses of covariance. Results The mean total number of medical comorbidities was 3.49 (standard deviation [SD] = 2.87; range, 0–16). The authors found a linear relationship between number of medical comorbidities and overall psychological distress (t[1, 959] = 16.79, P < .001) and interference owing to pain (t[1, 1,028] = 18.03, P < .001). Conclusions Patients with TMDs who have medical comorbidities may be at increased risk of experiencing poor psychological functioning. Further study is needed to investigate whether the observed relationship changes across time. Clinical Implications The physical and psychological health of patients with TMDs may influence the course of their pain condition. When treating these patients, dentists routinely should assess not only the symptoms of their TMDs but also their general health status.