Practicing clinicians appreciate that depression is not an easy disorder to treat and manage. Despite the plethora of new treatments-both pharmacological and non pharmacological-that has flooded the market in the past years, we are still nowhere close to obtaining full symptom relief for all patients and eradicating the morbidity and mortality associated with depression. In this context, recent methodological research, concentrating on the effectiveness of antidepressants has raised doubts about their therapeutic index. Because of obtuseness of the methodology and biased interpretations, we are submitting this perspective to clinicians so that they can appreciate some of the deficits of the recent research publications. For the practicing clinician, the best available data suggest that clinically depressed patients warrant treatment and the most robust available body of data (published and unpublished) would favor the use of antidepressants.