Depression is among the most prevalent and burdensome psychiatric disorders in the United States (Kessler et al., Achieves of General Psychiatry 62:617–627, 2005). There is substantial empirical support regarding efficacy of pharmacotherapy, psychotherapy, and combined treatment (both pharmacotherapy and psychotherapy) for treating depression. However, far less is known about the effectiveness of these treatments for real-world patients treated within routine clinical care settings (Cahill et al., The British Journal of Clinical Psychology 49:421–453, 2010). This study seeks to explore the effectiveness of treatment as usual (TAU) for depression in a large cohort of psychiatric outpatients receiving psychotherapy, pharmacotherapy, or combined treatment within an academic medical center. Initial and follow-up self-report assessments were analyzed for 1,322 patients receiving treatment for depression. Using these data, we determined treatment effect sizes, rates of reliable improvement (and deterioration), and rates of clinically significant improvement for psychotherapy, pharmacotherapy, and combined care. On average, all treatments produced significant improvement with effect sizes surpassing our no-treatment benchmark. No significant between-group (treatment) differences in self-report outcomes were found. The rates of reliable change were similar for all treatment groups consistent with past research. The present findings support the effectiveness of psychotherapy, pharmacotherapy, and combined treatment as routinely provided within a large academic medical center for the treatment of real-world patients suffering with depression.