Alda-1 is a potent and selective Aldehyde Dehydrogenase-2 Agonist. Alda-1 reverses alcohol-induced hepatic steatosis and cell death in mice. Alda-1 inhibits atherosclerosis and attenuates hepatic steatosis in apolipoprotein E-knockout mice. Alda-1 reduces cerebral ischemia/reperfusion injury in rat through clearance of reactive aldehydes. Pharmacological activation of ALDH2 by Alda-1 reversed alcoholic steatosis and apoptosis through accelerating aldehyde clearance. This study indicates that ALDH2 is a promising molecular target and Alda-1 has therapeutic potential for treating alcoholic liver disease.