The treatment of bipolar disorder remains a major challenge. A wide variety of psychopharmacological treatments are available, which are usually considered under the groupings of antimanic drugs, antidepressant drugs and mood stabilizers. In real-life clinical practice, monotherapy is the exception, and the challenge is to obtain rational polypharmacy. Even, with a wide range of available drugs, and a high likelihood of being able to achieve remission from any particular mood episode, the probability of recurrence and/or chronic residual symptoms is high. The greatest therapeutic challenges are in the areas of depressive and mixed symptom states.