The‘agent,’‘host,’and‘environment’of drug dependence are examined relative to their potential as effective foci of efforts in the areas of primary secondary and tertiary prevention. Factors associated with the agent and the host are shown to be of extremely limited value when it comes to the primary prevention of drug dependence. Results of prior rewards are reviewed and they serve as the basis for the conclusion that the manipulation of environmental factors holds the greatest promise relative to the primary prevention of drug dependence.