The “Coping with Depression” course (CWD) is by the far the best studied psychoeducational intervention for the treatment and prevention of depression, and is used in routine practice in several countries. The CWD is a highly structured cognitive-behavioral intervention, which has been adapted for several goals, contexts, and target populations. The efficacy of the CWD has been examined in 25 randomized controlled trials. We conducted a meta-analysis of these studies. The 6 studies aimed at the prevention of new cases of major depression were found to result in a reduced risk of getting major depression of 38% (incidence rate ratio was 0.62). The 18 studies examining the CWD as a treatment of depression found a mean effect size (Cohen's d) of 0.28. Direct comparisons with other psychotherapies did not result in any indication that the CWD was less efficacious. The CWD is a flexible treatment which can easily be adapted for different populations and this may have led researchers to use this intervention for complex target groups, which in turn may have resulted in a lower mean effect size. The CWD has contributed considerably to the development and innovation of prevention and treatment of depression in many target populations.