This paper is a systematic review of the available data concerning the treatment of bipolar disorder: a systematic Medline search concerning treatment guidelines and clinical trials. The search for treatment guidelines returned 583 articles and 913 papers for RCTs. The search was last performed on 1 March 2008. An additional search included repositories of clinical trials and previous systematic reviews in order to trace especially older trials. The literature suggests that lithium is useful during the acute manic and the maintenance phase. Both first- and second-generation antipsychotics are efficacious in the treatment of acute mania. Quetiapine and the olanzapine-fluoxetine combination are also effective for treating bipolar depression, while olanzapine, quetiapine and aripiprazole are effective during the maintenance phase. Anticonvulsants, particularly valproate and carbamazepine have antimanic properties, whereas lamotrigine may be preferably effective in the treatment of depression but not mania. Antidepressants should always be used in combination with an antimanic agent because they were reported to induce switching to mania or hypomania, mixed episodes, and rapid cycling when given as monotherapy. The best evidence-based psychosocial interventions for bipolar disorder are group- and family-focused psychoeducation. Electroconvulsive therapy is an option for refractory patients. Although a variety of treatment options for bipolar disorder is currently available, their effectiveness is far from satisfactory, especially against bipolar depression and maintenance. Combination therapy may improve treatment outcome but it also carries the burden of more side-effects. Further research as well as the development of better guidelines and algorithms for step-by-step rational treatment are necessary.