The present article explored two different dimensions of spirituality that might tap negative and positive relations with adolescent drug use over a 1-year period. Non-drug-use-specific spirituality measured how spiritual the person believes he or she is, participation in spiritual groups, and engagement in spiritual practices such as prayer, whereas drug-use-specific spirituality measured using drugs as a spiritual practice. Self-report questionnaire data were collected during 1997-1999 from a sample of 501 adolescents in 18 continuation high schools across southern California. Participants ranged in age from 14 to 19 and were 57% male, with an ethnic distribution of 34% White, 49% Latino, 5% African American, 7% Asian, and 5% other. A series of general linear model analyses were conducted to identify whether or not two different spirituality variables predict drug use (cigarettes, alcohol, marijuana, hallucinogens, and stimulants) at 1-year follow-up. After controlling for baseline drug use, non-drug-use-specific spirituality was negatively predictive of alcohol, marijuana, and stimulant use, whereas drug-use-specific spirituality failed to be found predictive of these variables one year later. Conversely, drug-use-specific spirituality was positively predictive of cigarette smoking and hallucinogen use, whereas non-drug-use spirituality failed to be found predictive of these variables. Our results provide new evidence that suggests that spirituality may have an effect on drug use among adolescents. The drug-use-specific measure of spirituality showed "risk effects" on drug use, whereas the other measure resulted in "protective effects," as found in previous research. Knowledge of the risk and protective patterns and mechanisms of spirituality may be translated into future drug use prevention intervention programs.