A substantial contribution of genetic factors to the risk of psychiatric disorders such as schizophrenia, bipolar disorder, autism, and drug and alcohol dependence has already been established. However, the familial transmission of these disorders cannot be explained by simple Mendelian models of inheritance, and non-genetic factors must also play a substantial role in their etiologies. Furthermore, the prevalence of any major psychiatric disorder is a great deal higher than that of Mendelian disorders. It has been suggested that evolutionary forces would rapidly eliminate large gene effects, which would suggest that mental disorders, which are highly prevalent, are associated with minor gene effects (Risch, 1994). The current paradigm is that genes with small interacting genetic effects, in conjunction with environmental factors, affect the risk for psychiatric disease. New laboratory and statistical methodology and database tools, and the availability of large clinical samples for the study of linkage and association sustain optimism that genes involved with these diseases will be characterized in the near future. This accomplishment should in turn lead not only to a better understanding of the primary molecular pathophysiology and to more specific and effective therapies, but also to a better understanding of non-genetic risk factors that could be targets for preventive strategies.