The author of the present article explores factors that account for variation in drug use and drug-related harm over time. A model of a drug system is presented, consisting of dependent variables, proximate causes and underlying determinants. The dependent variables concern drug use (level and pattern), adverse health consequences and drug-related crime. The major proximate causes of drug use and drug-related harm include drug availability (price and physical availability), attitudes towards use (fear of legal sanctions, health beliefs regarding risks and cultural beliefs) and alternatives to the illicit market (home cultivation and legal intoxicants for users, alternative career and income prospects for sellers). The underlying determinants that influence those proximate causes include policy (drug laws, preventive education and risk management programming) and environmental factors (geographical isolation, climate and fauna, and threat of acquired immunodeficiency syndrome (AIDS) and other infectious diseases). Despite recent improvements in the measurement of problematic patterns of drug use, there is still a paucity of data on patterns of use and drug-related harm. The viability of drug policy is thus often measured in terms of changes in levels of drug use and/or changes in the number of persons detected and charged with drug crimes. Until valid and reliable data are available on its key variables, any model of drug systems will have very limited applicability.