Although lithium is generally considered to be the gold standard for maintenance therapy in bipolar disorder, evidence of its efficacy has rested on only a small number of adequately designed studies. Results from the lamotrigine bipolar trials, which included lithium as an active comparator, will substantially increase confidence in long-term lithium treatment. In a meta-analysis of these data, lithium was significantly more effective than placebo in preventing relapse in patients with bipolar disorder (relative risk [RR] 0.65; 95% confidence interval [CI] 0.50, 0.84). Furthermore, lithium had significant efficacy against manic relapse (RR 0.61; 95% CI 0.39, 0.95), with a less substantial, not statistically significant, effect against depressive relapse (RR 0.72; 95% CI 0.49, 1.07). Factors such as disease subtype, likelihood of adherence to treatment regimen, tolerability, and dose uncertainty should be considered in the selection of lithium maintenance therapy. (C) 2003 Elsevier B.V./ECNP All rights reserved.