Platelet monoamine oxidase (MAO) activity has been shown to be inversely associated with personality traits such as sensation seeking, impulsiveness and extraversion. Those personality traits have also been linked to vulnerability for substance abuse, e.g. tobacco smoking and early onset or "type 2" alcoholism. Compounds in cigarette smoke have been shown to be inhibitors of MAO, which has led several authors to claim that there is no association between alcoholism, which is the most studied psychiatric condition, and platelet MAO if the effect of smoking is removed. With regard to the association between personality and platelet MAO, authors have in general been cautious. In the present paper we describe a number of results which show that there is such an association, both in clinical series if the effect of smoking is removed and in series where smoking have never taken place. A cornerstone in this regard is the significant association between platelet MAO activity and both behaviour/personality, voluntary alcohol intake and biochemical measures of CNS serotonergic activity in non-human primates. Strong evidence that the regulation of platelet MAO activity takes place on a transcriptional level with an involvement of transcription factors, likely to also regulate central monoaminergic activity, are presented.