The objective of this study was to gather data from a large group of clinicians on antidepressant prescribing practices in the treatment of refractory depression. Eight hundred and thirty-five clinicians about to attend the annual Massachusetts General Hospital psychopharmacology review course were asked to respond to a brief questionnaire regarding a hypothetical clinical case vignette. The case was of a patient who suffered from a new onset, unipolar, nonpsychotic, severe major depressive episode. Three hundred and four (36%) clinicians agreed to participate and filled out our questionnaire. Of the respondents, 260 (85.5%) indicated their preference for an initial treatment that combined medication and psychotherapy, as opposed to either modality alone. Furthermore, given this patient's nonresponse to two adequate selective serotonin reuptake inhibitor (SSRI) trials and one atypical antidepressant trial over an 8-month period, 39.8% of respondents indicated venlafaxine monotherapy as their next choice, whereas combining antidepressants (20.1%) and augmentation (18.4%) were the second and third most preferred treatment choices at this time point. Further on in the course of treatment, with the patient not having responded to any interventions during a 16-month period, 80.9% of survey respondents indicated electroconvulsant therapy (ECT) as their next preference. Among 304 clinicians surveyed, a combination of therapy and medication is the most preferred choice for treating severely depressed outpatients with new onset depression. Switching to venlafaxine, using two antidepressants together, and augmentation of an antidepressant regimen with a second agent accounted for 78.3% of respondents' preferences when faced with treating a depressed patient who had not responded to two adequate SSRI trials and one adequate atypical antidepressant trial. Of the respondents, 80.9% indicated ECT as a treatment preference after 16 months of multiple failed medication trials and nonresponse to psychotherapy. Further research is necessary to elucidate the factors that influence clinicians' reasoning for selecting one strategy over another.