Depressive and bipolar disorders (BPD) are among the greatest challenges to mental well-being and are diagnosed in increasing numbers despite advances in research and treatment. The preponderance of the evidence suggests that BPDs and severe unipolar depression have strong biological hereditary origins and benefit from psychopharmacological intervention as well as other medical treatments such as electroconvulsive therapy. The best results, however, involve a combination of medical and psychosocial treatments; in mild to moderate depression, the efficacy of cognitive behavior therapy and interpersonal therapies is proven beyond that of medication. The addition of the Intersectionality/Resiliency Formulation to the Diagnostic and Statistical Manual of Mental Disorders diagnostic system, with its attention to internal and external sources of resiliency, ensures that attention is systematically paid to the patient's unique identity and his salient personal contexts.