This updated version of the bipolar depression algorithm of the Psychopharmacology Algorithm Project at the Harvard South Shore Program aims to provide an organized, sequential, and evidence-supported approach for the treatment of that disorder. After initial evaluation and diagnosis, the psychiatrist should first assess whether there is an urgent indication for ECT. If ECT is not indicated, and the patient has psychotic symptoms, then an antipsychotic should be part of the medication regimen. Next, if the patient is not currently treated with mood stabilizers, there is a slight preference for lithium. If lithium is not effective or tolerated, treatment with quetiapine or lamotrigine should be initiated. If the patient is currently taking other mood stabilizers, their dosage should be optimized, and the clinician should consider adding or switching to lithium, quetiapine, or lamotrigine. Next, if the patient is not at especially high risk of mood destabilization, an antidepressant can be added in the bipolar depressed patient who has failed trials of lithium, quetiapine, and lamotrigine. Rapid-cycling depressed patients may require combinations of two or three mood stabilizers. ECT, along with other psychopharmacological options, could be reconsidered for the treatment of refractory bipolar depressed patients.