As researchers make progress in elucidating the roles of specific genes that contribute to the risk of alcohol dependence, they also need to understand how the interplay between genetic and environmental risk factors increases risk. The term "genotype x environment (GxE) interaction effect" refers both to the modification of genetic risk factors by environmental risk and protective factors and to the role of specific genetic risk factors in determining individual differences in vulnerability to environmental risk factors. Understanding the contributions of GxE interaction effects to the risk for and development of alcohol dependence and coexisting disorders is of paramount importance. These GxE interaction effects can be determined by appropriately designed family and molecular epidemiological studies, such as studies of children of twins and prospective family studies.