This is the first remarkable results of the treatment of manic patients with lithium were published 60 years ago and to date lithium remains one of the most important psychotropic medications. In this special issue, research on clinical characteristics of persons prophylactically treated with lithium as well as the evolution of an outpatient setting providing long-term lithium therapy are presented. The most important clinical properties of lithium, such as prevention of affective recurrences, augmentation of antidepressants in treatment-resistant depression, and anti-aggressive and anti-suicidal effects are reviewed. Further, the neurobiology and pharmacogenetics of lithium are summarized and a report on the most recent international initiative aiming at performing a geme-wide association study in lithium-treated patients completes this issue. Psychiatrists, psychologists, and neurobiologists interested in optimal pharmacological treatment of patients with mood disorders and in the pathogenesis of such conditions will find up-to-date information in this special issue. Likewise it will be interesting reading for bipolar patients, their relatives and caregivers.