Bipolar depression remains one of the most challenging conditions for clinicians to accurately diagnose and effectively treat. For hospitalized patients with bipolar disorder, mood stabilizers--a term often used by clinicians to denote medications that treat acute manic, hypomanic, and depressive symptoms--are often used as first-line treatment. Despite the short- and long-term benefit of a mood stabilizer, comorbid factors, such as substance abuse, can affect patient treatment response. Thus, once the patient's mood is stable and diagnosis is confirmed, clinicians should work with patients on hospital discharge planning, including outpatient follow-up and psychosocial education. In addition to preventing bipolar depression relapse, outpatient initiatives may focus on substance abuse or other comorbid factors. In order to make an accurate diagnosis of bipolar depression, clinicians should perform a complete assessment of the patient and the patient's family at presentation as well as determine whether symptoms are due to bipolar type I disorder or bipolar type II disorder. Presence of substance abuse may complicate initial assessment as patients may be experiencing symptoms related to abuse, including withdrawal. Beyond mood stabilizers and atypical antipsychotics, which should be optimized and chosen based on the treatment history of the patient, antidepressants offer another treatment option for bipolar depression, although they should not be used first line or as monotherapy. As substance abuse often occurs comorbid with bipolar depression, both problems should be addressed with a treatment plan. This expert roundtable supplement addresses the course of diagnosis and treatment for hospitalized patients with bipolar depression and presents a case study to demonstrate clinical challenges related to bipolar patients. The onset and severity of bipolar depression, prevalence of substance abuse, psychosocial treatment options, and clinical issues for the long-term treatment of bipolar depression are also discussed.