The Sequenced Treatment Alternatives to Relieve Depression (STAR( *)D) study addressed many clinically relevant issues on treatment of depressed outpatients. The study used an equipoise-stratified randomization scheme that enhanced the real-world expediency of treatment options studied. Because patients who had significant comorbid medical and psychiatric problems were included, and care was provided in the outpatient primary care setting as well as in outpatient psychiatric centers, findings are relevant to primary care physicians. The use of measurement-based treatment protocols promotes objectivity in a realm of often subjective clinical decision making. Although STAR( *)D was unable to provide specific treatment comparisons for patients at all study levels, it succeeded in defining the prevalence of treatment-resistant depression and is a model for further practical clinical outcomes studies.