The aim of this study was to compare the effects of weight loss treatment, cognitive-behavioral treatment, and desipramine on binge eating and weight in a three group additive design involving 108 overweight participants with binge eating disorder. Subjects were allocated at random to either 9-months weight-loss-only treatment; 3-months of cognitive-behavioral treatment followed by weight loss treatment for 6-months; or the combination treatment with desipramine added for the last 6-months. After 3-months of treatment, those receiving cognitive-behavioral therapy had reduced binge eating significantly more than participants receiving weight loss therapy only, and the weight loss only group had lost significantly more weight than those in the cognitive-behavioral groups. The addition of medication did not lead to greater reductions in the frequency of binge eating. Hence, there was no evidence that either cognitive-behavioral therapy or desipramine added to the effectiveness of weight loss therapy. However, those receiving medication lost significantly more weight than the comparable group without medication at follow-up. Abstinence from binge eating was associated with significantly greater weight losses. Overall, however, the achieved weight losses were small and the abstinence rates low. Moreover, there were no differences between the three groups either at the end of treatment or at follow-up. Suggestions for further research aimed at improving the therapeutic results for this difficult clinical problem are discussed.