Background: During over half a century, science has shown that lithium is the most efficacious treatment for bipolar disorder but despite this, its prescription has consistently declined internationally during recent decades to approximately 35% ever use or less of patients with bipolar disorder. Content: This narrative review provides an overview of the decreasing use of lithium in bipolar disorder internationally, shortly summarises the evidence for lithium’s acute and prophylactic effects in bipolar disorder, discuss the challenges in relation to lithium including side effects, long-term risks and myths around lithium and provides two detailed examples on how specialised care models may result in successful increase of the use of lithium to 70% of patients with bipolar disorder largescale and improve care regionally and nationally. Conclusions: Decades of scientific investigations and education and teaching of clinicians and the public has not increased the use of lithium on a population-based large scale. It is argued that lithium should be the drug of choice for maintenance therapy as the single first-line treatment and that organizational changes are needed with specialised care for bipolar disorder to systematically and long-term change the use of lithium on a large-scale population-level.