A wealth of pharmacological data point to the involvement of catecholamine metabolism in a number of psychiatric and behavioral disorders. Furthermore, evidence points to many of these affective disorders having a moderate to large genetic component. These observations have provided the impetus to search for differences between individuals in the structure and regulatory elements of genes involved in catecholaminergic neurotransmission. The recent finding that a mutation in the structural gene for the enzyme monoamine oxidase A is associated, in several males of a large kindred, with borderline mental retardation and abnormal behavior is an important breakthrough in the field. Other promising results concern the tyrosine hydroxylase gene in manic depressive illness and the dopamine D2 receptor in alcoholism. These studies, their potential significance and difficulties in dealing with such complex disorders are discussed.