Current cigarette smokers have reduced monoamine oxidase (MAO) and there is evidence that this is a pharmacological effect of tobacco smoke exposure rather than a biological characteristic of smokers. This article summarizes human and animal studies documenting the inhibitory effects of tobacco smoke on MAO and discusses MAO inhibition in the context of smoking epidemiology, MAO inhibitor compounds in tobacco, reinvestigations of low platelet MAO in psychiatric disorders and smoking cessation.