This chapter reviews the data and their interpretation in an attempt to characterize the range of reactions in humans to alcohol and, where possible, to consider the way genetic factors influence the form and/or patterns of such reaction. Most work in the area of genetic factors associated with tolerance of and dependence upon alcohol is found in reports of animal study. Studies of genetic factors in the natural history of the consequences of alcoholism should include evaluation of sex and psychopathology in the proband and history of alcoholism in the family. G.E. Barnes concluded that there were few findings to suggest a precursor alcoholic personality and that the personality pattern noted in clinical alcoholism is most likely a response to the process of addiction and the effects of prolonged alcohol use. Genetic factors contribute to metabolism, degradation, and elimination of alcohol but explain patterns of heavy drinking.