Laboratory models, including animal tissues and live animals, have proven useful for discovery of molecular targets of alcohol action as well as for characterization of genetic and environmental factors that influence alcohol's neural actions. Here we consider strengths and weaknesses of laboratory models used in alcohol research and analyze the limitations of using animals to model a complex human disease. We describe targets for the neural actions of alcohol, and we review studies in which animal models were used to examine excessive alcohol drinking and to discover genes that may contribute to risk for alcoholism. Despite some limitations of the laboratory models used in alcohol research, these experimental approaches are likely to contribute to the development of new therapies for alcohol abuse and alcoholism.