The article by Hollon and colleagues1 in this issue of JAMA Psychiatry describes the main findings of one of the most important studies ever undertaken to evaluate the merits of combining psychotherapy and pharmacotherapy for treatment of major depressive disorder (MDD). This randomized clinical trial (RCT) compared the outcomes of patients who received the Beck model of cognitive therapy (CT) in combination with a flexible, algorithm-guided pharmacotherapy protocol vs those who received pharmacotherapy alone. The study is important because of the topic—MDD is one of the world’s great public health problems and the combination of psychotherapy and pharmacotherapy has long been advocated as a preferred approach to optimize outcomes—and the approach taken, a large-scale (N = 452), 3-center study with adequate power to test both main effects and possible interactions across both short-term and continuation phases of study treatment. Thus, unlike the conventional, more narrowly focused, and smaller-scale RCT, which might be delimited to comparing response rates across 8 to 16 weeks of randomized treatment, clinicians in the current study could make multiple adjustments in the treatment regimen across up to 19 months to achieve remission, and during up to 42 months of continuation therapy to prevent relapse and foster recovery.