Adherence to drug therapy is a limitation in treatment success for major depressive disorder (MDD). The influence of RHYTHMS, an information and ongoing interactive program designed by Pfizer Pharmaceuticals, to address patient adherence to sertraline therapy was evaluated in a primary care setting using a randomized, double-blind, parallel group controlled trial over 29 weeks. Remission was the primary outcome evaluated. At study completion, no statistically significance between group differences was noted for remission rates, treatment adherence or mean Hamilton Depression Rating Scale (HDRS) score. However, the RHYTHMS group reported significantly greater satisfaction with knowledge received about depression and its treatment and demonstrated significantly greater satisfaction with treatment received. We conclude that the application of RHYTHMS in a primary care setting has a substantial role in improving satisfaction with sertraline treatment by patients with MDD.