STAR*D is valuable because it examines, in a systematic way, response and remission in a sequential approach for those patients who do not remit with standard treatment. Furthermore, it is valuable because it avoids some of the limitations in generalizability and external validity of most previous studies. It has also added some novel findings to the literature from which we derive our clinical guidance, but in the end, this first wave of data from STAR*D will not greatly affect the prescribing practices of most clinicians. The study has confirmed much of what we suspected, based on industry and federally sponsored clinical trials, case reports, and expert opinion. STAR*D does not answer all of our questions, but progress in science is incremental, and STAR*D has added incrementally to the evidence base for the use of antidepressants. However, while it is asking too much of any study, we are left wanting more—more attention to other current options, more certainty, and, in the end, more guidance.