Self-system therapy (SST) is a new therapy based on regulatory focus theory (E. T. Higgins, 1997) for depressed individuals unable to pursue promotion goals effectively. The authors conducted a randomized trial comparing SST with cognitive therapy (CT) in a sample of 45 patients with a range of depressive symptoms to test 2 hypotheses: that SST would be more efficacious for depressed individuals characterized by inadequate socialization toward pursuing promotion goals and that SST would lead to greater reduction in dysphoric responses to priming of promotion goals. There was no overall difference in efficacy between treatments, but patients whose socialization history lacked an emphasis on promotion goals showed significantly greater improvement with SST. In addition, SST patients showed a greater reduction in dysphoric responses to promotion goal priming than did CT patients. The results illustrate the value of a theory-based translational approach to treatment design and selection.