Mood elevation, which includes mania, hypomania, and mixed states, was previously considered the defining symptom of bipolar disorder, but bipolar depression by comparison is actually a much more substantial challenge to diagnose and treat. Recent studies, including research by the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), found that patients with bipolar disorder spend longer periods of time in depressive episodes and are more likely to relapse to depression compared with mania or hypomania. However, the treatment of bipolar depression is hampered by the limited number and varying quality of available studies of pharmacologic treatments to guide clinical decision making. Clinicians should rely on studies with the highest level of evidence (category A) when prescribing appropriate antidepressant treatments. The standard care pathways outlined by STEP-BD to aid clinicians in treating varying phases of bipolar disorder provide data on the use of various treatments for bipolar depression and their outcomes. While some treatments have the potential to induce mania, others appear to have some efficacy without inducing mania.