The mood stabilizers lithium, valproate and lamotrigine are traditionally used to treat bipolar disorder. However, accumulating evidence suggests that these drugs have broad neuroprotective properties and may therefore be promising therapeutic agents for the treatment of neurodegenerative diseases, including stroke. Lithium, valproate and lamotrigine exert protective effects in diverse experimental stroke models by acting on their respective primary targets, ie, glycogen synthase kinase-3, histone deacetylases and voltage-gated sodium channels, respectively. This article reviews the most recent findings regarding the underlying mechanisms of these phenomena, which will pave the way for clinical investigations that use mood stabilizers to treat stroke. We also propose several future research avenues that may extend our understanding of the benefits of lithium, valproate and lamotrigine in improving stroke outcomes.