Depression is the most commonly diagnosed mental illness in the United States with relapse rates as high as 80–90% in some circumstances. Cognitive therapy (CT) and psychopharmacology have been the mainstays of treatment for depression and relapse prevention, yet relapse remains a significant risk of this mental illness. The literature review, case illustration and analysis examines the rationale for integrating mindfulness practice, and demonstrates the application of this practice in conjunction with cognitive therapy to reduce the risk of relapse in Major Depression.