This presentation on managing bipolar depression and mixed presentations reviews the dimensional continuum of mood disorder presentations from unipolar to bipolar disorder, evidence supporting the use and limitations of mood-stabilizing drugs and second-generation antipsychotics for the treatment of unipolar and bipolar depression, limitations of monoaminergic antidepressants in bipolar depression and major depression with mixed features, and evidence-based patient treatment plans based upon patient and disease state-specific characteristics.