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In this study, we reviewed data on drug use among high school students in Iran.Published epidemiological studies in international and domestic journals show that drug use/abuse is a serious mental health problem in Iran. There is cultural support for opium in Iran and also there is cultural tolerance for tobacco smoking, especially as water pipe smoking in Iranian families. Alcohol, opium and cannabis are the most frequently used illicit drugs, but there are new emerging problems with anabolic steroids, ecstasy and stimulant substances, such as crystal methamphetamine.There is a serious drug abuse problem among Iranian high school students. It could be due to role modeling by parents – mainly fathers – and also cultural tolerance of some substances. Early onset of tobacco smoking, with a daily use rate between 4.4 and 12.8% in high school students, is an important risk factor for other drug abuse problems. Use of all types of drugs, except prescription drugs, is more prevalent among boys. Alcohol is the most frequently abused substance, with a lifetime rate of at least 9.9%. Lifetime rates of opiate use – mostly opium – was between 1.2 and 8.6% in different parts of the country. As drug abuse is a frequent problem among Iranian high school students, it is necessary to design and implement drug prevention programs to protect them. Such programs, including life skills training and drug education, have been operating in recent years for Iranian students from kindergarten to the university level.