The episodic and chronic nature of bipolar disorder usually requires long-term treatment in all patients, yet there is an unmet need for well-tolerated and clinically effective maintenance therapy with enhanced patient adherence. Few well-tolerated treatment options are currently available that are both effective in all phases of bipolar disorder and prevent recurrence of episodes. Lithium has well-established efficacy in the prevention of further manic episodes and may also be effective in the prevention of depression and suicide, but safety is a concern due to narrow therapeutic window. For valproate and carbamazepine, data appear much less compelling. Lamotrigine has shown to be effective for long-term prevention of depressive episodes. Controlled studies suggest that atypical antipsychotics may also have mood-stabilizing properties and might become standard for long-term therapy in the new future. The role of psychoeducation in improving adherence to medication in long-term treatment and overall patient outcomes is also crucial.