Lithium has been used for the medical treatment of bipolar disorder for over 50 years. The purpose of this paper is to review the evidence base supporting the use of lithium in the maintenance phase of treatment of bipolar disorder and the limitations which reduce the clinical effectiveness of this medication. A selective review of the relevant literature was carried out. It is concluded that lithium is efficacious in the maintenance phase treatment of bipolar disorder, with the available evidence supporting a beneficial effect which prevents recurrence of mania; it is less clear if lithium prevents depressive episodes in bipolar disorder. A number of lines of evidence support the notion that lithium reduces suicidal acts and completed suicide. Lithium has a significant side effect burden and a narrow therapeutic index. It is also associated with an increased liability for new episodes, both manic and depressive, consequent upon stoppage of treatment. These factors limit the clinical effectiveness of lithium.