Social/recreational rewards ("to get high," "to have a good time," and "to experiment" with drug effects) were most often cited as reasons for using most drugs; however, the reasons most often given for using psychotherapeutic drugs pertained to coping with negative emotions and physical needs. Significant differences in reported reasons for using drugs were found between boys and girls; boys were more likely to report social/recreational and drug-effect reasons for using substances; whereas, girls were more likely to report using drugs to cope with negative emotions and physical needs. Significant differences by race/ethnicity were also found; White drug users were somewhat more likely to report social/recreational reasons for drug use, and minority racial/ethnic youth were more likely to report addictive reasons for using specific substances. Findings suggest that prevention strategies should focus on nondrug alternatives for having a good time and/or feeling good. Research on the effects of anti-tobacco messages indicate that the most powerful prevention messages may be those that accurately and directly address the harms associated with the use of specific substances. The promotion of constructive strategies for coping with negative emotions and physical needs could also divert youth from relying on drugs to address these needs. The obtained total weighted sample size used in the current analyses was 75,515 12th graders. All of these youth answered survey questions about their reasons for using drugs. The drugs cited in the questioning were alcohol, barbiturates, tranquilizers, narcotics other than heroin, amphetamines, and cocaine. 13 tables, 12 figures, and 46 references