Genetic factors play a role in alcohol dependence with a heritability of over 50%, but since alcoholism is a multifactoial disease, overall, there is no clear pattern of Mendelian inheritance. Family studies indicate that both genetic and environmental factors play a role in alcohol dependence. Individuals with genetic variants in alcohol metabolizing enzymes that result in increased acetaldehyde levels following alcohol have a dysphoric response to alcohol ingestion and are protected from developing alcoholism. In some instances genetic variation in the neurobiologic pathways involved in alcohol pathophysiology have been found to relate to some alcohol effects and the development of alcohol dependence and its response to treatment. Variations in genes that result in decreased availability of dopamine D2 receptors increase the risk of alcohol and substance use and relate to some treatment effects. Genetic variations in the GABA A receptor alpha 2 sub unit are associated with alcoholism, reduce subjective effects of alcohol and relate to treatment. Genetic variations in the opioid u receptor gene alter alcohol induced “high” in heavy drinkers and the treatment response of alcohol dependent individuals to naltrexone. Stress increases alcohol drinking and genetic variations that increase activity in the CRF system increase alcohol intake. Gene variants in the glutamate system relate to alcohol use. A genetic variant that decreases endocannabinoid metabolism is associated with problem drug and alcohol use, and variations of the nicotine receptor gene relate to decreased objective and subjective effects of alcohol and increased number of drinks to reach a desired effect.