A review of the literature on the relationships between alcoholism, personality, and religion identified patterns that may help explain the inverse association between alcoholism and religion/spirituality (R/S). Personality plays a central role in two etiological models of alcoholism. The personality traits of high behavioral undercontrol (low Agreeableness and low Conscientiousness) and high negative affect (high Neuroticism) are both significantly related to higher alcohol use. Religiosity is also correlated with these traits, but in the opposite direction (e.g., with low behavioral undercontrol and low negative affect). Thus, the personality profiles associated with alcoholism and religion are the inverse of one another. In addition, evidence suggests that R/S moderates genetic variation on both Neuroticism and Disinhibition (part of behavioral undercontrol). Implications are discussed in terms of competing explanatory models: a basic research model which argues for genetically-determined stability in personality and alcoholism risk, and a clinical treatment model which argues for the primacy of environmental interventions in treatment and the possibility of personality change as a pathway to recovery.