Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet etiologic factors contributing to the disorder remain obscure. Complex psychiatric disorders may be influenced by a number of genes that may be difficult to detect because each has a small effect on a disorder that is broadly defined within a social context. However, such genes might be detected if they have a major effect on a more narrowly defined phenotype. Underlying alcohol dependence are appetitive drive states or instincts that lead to drug 'craving', contribute to compulsive drug usage, and influence relapse following abstinence. A whole genome scan in Mission Indian families provides evidence for genetic linkage to 'craving for alcohol' on chromosome 5. Identification of genes contributing to alcohol craving may give clues to the etiology of the disorder and also provide targets for the development of new medications to treat alcohol dependence.