Despite major research efforts in mood disorders, careful scientific studies and evaluations of "treatment resistant depression" (TRD) are limited. Treatment resistant depression often encompasses several conflicting definitions and concepts: (1) the distinction between 'absolute' TRD and 'relative' TRD is seldom made; (2) the combination of a dysthymic disorder and a major depression ("double depression") can lead to diagnostic confusion when one disorder improves while the similar symptoms of the other persist; and (3) the literature becomes confused when ineffective prophylaxis and ineffective acute treatment are not separated. The research at our Center continues to suggest that the primary problem in this area remains 'relative' TRD. In a recent study of 114 patients referred to our Mood Disorders Service with a diagnosis of TRD, 59 of 98 (60.2%) had complete depressive symptom remission with appropriate treatment interventions. Further, the majority of these 59 successful treatment interventions were the 'bread and butter' treatments available to all physicians; 9 (15.3%) patients responded to an adequate trial of a tricyclic, 12 (20.3%) to a monoamine oxidase inhibitor, and 17 (28.8%) to a course of electroconvulsive therapy.