With the last two decades, the importance of genetic factors in the aetiology of major mental illness has been firmly re-established and psychiatric research has now firmly embraced the era of molecular genetics. Despite a number of false starts in the study of schizophrenia and affective disorder, there have been successes in unmasking some of the aetiological secrets of Alzheimer's disease. We will give an overview of the rationale behind these studies and the major findings to date.