Clinicians are faced with a diagnostic challenge when a bipolar patient reports breakthrough depressive symptomatology. Breakthrough depressive symptoms during treatment for a bipolar depressive episode may be a manifestation of recurrent bipolar depression or the emergence of a mixed episode. Treatment of recurrent bipolar depression and mixed episodes differs considerably, and antidepressant therapy during a mixed episode can worsen the episode and initiate or exacerbate rapid cycling. Therefore, accurate diagnosis and appropriate treatment are imperative to achieving a positive outcome. Research indicates that optimizing the current mood stabilizer therapy or adding another mood stabilizer may be the best treatment options for patients with a history of rapid cycling-in patients without a history of rapid cycling, adding an antidepressant to a mood stabilizer may be less risky and therefore a reasonable choice. Combination therapy with a mood stabilizer and an atypical antipsychotic may also be effective in managing bipolar depressive episodes.