The history of research on the association between platelet monoamine oxidase (MAO) activity and personality traits, such as sensation seeking and impulsiveness, is reviewed. The effects of MAO-inhibiting compounds in cigarette smoke for the interpretation of this association are discussed. Recent results confirming a true association between platelet MAO activity and personality are presented. From a clinical point of view, this association has had its greatest impact on the understanding of the nature of constitutional factors making individuals vulnerable for e.g. substance abuse and the link between low platelet MAO activity and type 2 alcoholism, recently confirmed on non-human primates, is discussed. The molecular mechanisms underlying the association between platelet MAO and behaviour are discussed and evidence that common transcriptional factors, e.g. within the AP-2 family, regulating both the expression of platelet MAO and components of central monoaminergic systems, such as synthetizing enzymes, receptors and transporters, are presented. A hypothesis is put forward, that such common transcription factors may not directly regulate platelet MAO expression, but rather mitochondrial number or outer membrane surface.