This study examined rationales for alcohol, marijuana, and other drug use among Indian and non-Indian youth. Differences were found between reservation Indian and rural non-Indian rationales for alcohol, marijuana, and other drug use. A majority of both Indian and non-Indian eighth graders indicate that they use drugs to enhance positive affective states, for excitement, for parties, to be with friends, to relax, and to handle negative affective states including worries and nervousness. Indian youth appear to also use drugs to cope with boredom. Unlike non-Indian youth, Indian youth have no strong rationales for their use of other drugs. Interventions will have to be impactful and pervasive in order to counter the many positive and negative rationales associated with drug use.