Lithium has been the drug of choice in treating bipolar disorder for 50 years and, therefore, patterns of response associated with its use define what we expect from treatment. Although efforts to establish some other agents as antimanic have been successful, it is difficult to assess their overall efficacy in relation to that of lithium without a better understanding of inclusion/exclusion criteria, subtypes, definitions of remission, relapse and recurrence, and duration of study. All of these factors need to be carefully addressed to identify the most important clinical targets for new drug development. Additional relevant information emerges from studies on combinations of mood stabilisers, efficacy of antimanic agents in different patient populations, analysis of rates of drop-out, non-compliance, suicide, drug abuse, and discontinuation especially with long-term treatment. Agents other than lithium that are effective in the acute phase treatment are still not well characterised as mood stabilisers. New agents need to be evaluated in the context of long-term treatment and the targeting of specific components of the syndrome beyond mania.