Depression is usually the predominant phase in bipolar disorder, causes the most psychosocial disability, and carries significant risk of suicide. The management of bipolar depression is relatively under-studied and poses significant challenges for clinicians. There is substantial dissent regarding optimal pharmacotherapy for bipolar depression, particularly around the role of antidepressants. Individual and combination pharmacotherapy should be integrated into a personalised psychosocial and lifestyle package of interventions that considers the person's clinical profile and preferences. The relative lack of evidence relating to optimal strategies, especially when bipolar depression occurs with common comorbidities, poses challenges and requires further research. A flexible approach and evidence-based combinations of treatments can provide effective strategies for improving quality of life and reducing morbidity and mortality.