Objective: We reviewed important clinical aspects of bipolar depression, a progressive psychiatric condition that is commonly treated in primary care. Bipolar depression is associated with considerable burden of illness, high suicide risk, and greater morbidity and mortality than bipolar mania. Methods: We identified articles relevant to our narrative review using a multistep search of the literature and applying terms that were relevant to bipolar depression or bipolar disorder. Results: Bipolar depression accounts for the majority of time spent unwell for patients with bipolar disorder; high rates of morbidity and mortality arise from full symptomatic episodes and interepisode subsyndromal symptoms. Bipolar depression is an important contributor to long-term dysfunction for patients with bipolar disorder due to psychosocial impairment, loss of work productivity and high rates of substance abuse. Missed and delayed diagnosis is prevalent due to overlapping symptoms with unipolar depression and other diagnoses. Medical comorbidities (i.e. cardiovascular disease, hypertension, obesity, metabolic syndrome) and psychiatric comorbidities (i.e. anxiety disorder, personality disorder, eating disorder, attention-deficit/hyperactivity disorder) are common. Currently, only three treatments are FDA-approved for bipolar depression; monotherapy antidepressants are not a recommended treatment option. Conclusions: Bipolar disorder is common among primary care patients presenting with depression; it is often treated exclusively in primary care. Clinicians should be alert for symptoms of bipolar disorder in undiagnosed patients, know what symptoms probabilistically suggest bipolar versus unipolar depression, have expertise in providing ongoing treatment to diagnosed patients, and be knowledgeable about managing common medication-related side effects and comorbidities. Prompt and accurate diagnosis is critical.