This article reviews the main outcome findings from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The study compared the efficacy and tolerability of a range of antidepressant therapies through four sequential levels of treatment with the goal of achieving remission. Remission rates based on the primary outcome measure (Hamilton Rating Scale for Depression) were 28% (Level 1 citalopram), 17% to 30% (Level 2 treatments), 12% to 25% (Level 3 treatments), and 7% to 14% (Level 4 treatments). For patients not responding adequately to an initial trial of citalopram, subsequent treatment strategies may be effective. When more treatment steps are required, however, lower acute remission rates, greater degrees of treatment intolerance, and higher relapse rates during follow up are seen. There were few differences among treatments within each level related to efficacy or tolerability, although patients had clear preferences for or against certain treatments.