Objective: It is widely acknowledged that the prevalence of depression in the general population is high, but that it is even higher for patients with medical disorders. Yet, the effectiveness of psychological treatments in these patient populations has not been firmly established. Methods: We conducted a meta-analysis of randomized controlled studies examining the effects of psychological treatments in patients with 1 of 10 different medical disorders and elevated levels of depression. Extensive searches were performed in PubMed, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials. Results: We included 23 studies. The overall effect size of the 15 studies that compared psychological treatments with a waitlist or care-as-usual control group was d=1.00 [95% confidence interval (CI), 0.57-1.44] but declined to d=0.42 (95% CI, 0.27-0.58) after removing two outliers with extremely high effects. We tested the type of disorder, inclusion based on diagnostic criteria or symptoms, type of treatment, treatment format, type of control group, and intention-to-treat or completers analyses, but none of these variables were significantly associated with the effect. The four studies that compared one type of psychotherapy to another showed a positive effect of cognitive behavioral therapy and interpersonal therapy compared to supportive therapy (d=0.42; 95% CI, 0.14-0.69). There were not enough studies (n=3) to draw any conclusions about the comparison of psychotherapy to pharmacotherapy. Conclusion: We conclude that the effects of psychological treatment of patients with medical disorders are very similar to those found in otherwise healthy patients. Treating this comorbid depression should be one of the priorities in medical care settings. © 2010 Elsevier Inc.