Bipolar disorder is difficult to treat. There are several options to treat acute mania, but combination of two or more drugs is the rule rather than the exception, indicating the limitations of currently available therapies. The evidence base for the treatment of bipolar depression is much weaker, and again combination is the rule. Although patients with bipolar disorder may experience resolution of symptoms with acute treatment, many will continue to experience impaired functioning due to the episodic, chronic, and progressive nature of the illness. Maintenance therapy is needed for a variety of reasons, including prevention of relapse, reduction of subthreshold symptoms, decreasing the risk of suicide, and reducing the frequency of rapid cycling and mood instability. Although long-term therapy is usually required to maintain or improve functioning and quality of life, it has been a significant challenge to identify clinically effective treatments for long-term management. There are few currently-available, well-tolerated treatment options that are effective in all phases of bipolar disorder and which prevent recurrence of manic and/or depressive episodes. Questions concerning when to discontinue one of the drugs when two or more are used, or how to switch from one mood stabilizer to another, have not been addressed in clinical trials. Electroconvulsive therapy may be effective in treatment resistant cases and can be used as maintenance when pharmacotherapy is not enough. Psychoeducation may help to enhance treatment adherence and healthy lifestyle. A rational combination of the above mentioned strategies may help to optimize the outcome of this challenging condition.