Recent studies with MAO B inhibitors do not support the notion of neuroprotective actions by direct inhibition of the isoenzyme nor by inhibition of MAO A. MAO activity is present in the brain in large amounts. MAO B is increased in Parkinson’s disease (PD) due to gliosis and in smokers by a compensatory mechanism for the inhibition of the enzyme by compounds contained in tobacco smoke. Both isoenzymes should be inhibited to a certain extent to achieve neuroprotection by decreasing the production of detrimental reactive oxygen species (ROS). The correlation between the levels of the bCs norharman (inhibitor of MAO B) and harman (inhibitor of MAO A) in tobacco smoke and the proportion of the inhibited isoenzymes in the human brain measured by PET strongly support the notion that these two bCs are responsible for the inhibition of MAO A and B in human brain from smokers. Epidemiologic studies show that smoking subjects have a reduced risk for developing PD. Studies using in vivo microdialysis and electrophysiology demonstrate a preference of the bCs for dopamine neurons. Provided smoking a full cigarette results in more than 88% nicotinic receptor occupancy associated with desensitization of these receptors, we postulate that the bCs contribute substantially not only to the neuroprotective actions of smoke with a reduced risk for PD but also to the addictive effects specifically to improve mood and pleasure. Keywords Monoamine oxidase A • Monoamine oxidase B • Norharman • Harman • Neuroprotection • Smoking • Nicotinic receptor • Parkinson’s disease • Addiction