Nonpsychotic depressive and dysthymic states are reclassified and reorganized in order to maximize relevance to clinical psychopharmacology. In the initial phase of assessment, patients are divided into two easily recognized categories: moodnonreactive (autonomous) depression and mood-reactive depression. After family and past history of response and cost of drug are considered, a tricyclic antidepressant is usually selected for autonomous depression patients, and mood-reactive depression patients are initially given a serotonin reuptake inhibitor. Nonresponders from either category are changed to the alternative medication or have it added to their first drug. Nonresponders to both of these initial trials are then assessed for the presence of atypical depression symptoms by the Columbia criteria. If these symptoms are present, the patients may be offered a third medication trial with a monoamine oxidase inhibitor. Bupropion could be the choice if the monoamine oxidase inhibitor cannot be given expeditiously. This completes the initial assessment and treatment phase.Autonomous and mood-reactive patients who do not respond to this sequence of interventions are then reassessed for the presence of characterologic syndromes and comorbidity with some frequently encountered conditions. These may determine the choice of medication and the prognosis for a positive result from the next choices selected. When possible, specific recommendations are given for the various situations.