Problems related to homeless/runaway youths have received increased attention in recent years. Homeless/runaway youths manifest many problems in addition to being absent from home and without supervision of a parent or guardian. The purpose of the study was to determine drug use and abuse patterns of homeless/runaway youths and to compare those patterns, along with attitudes toward selected illicit behaviors, with similar data collected from adolescents in school. Data were collected from persons (n = 253) in homeless/runaway shelters in the southeast United States. Comparisons made with data from other studies of runaways and of youths in school indicate that drug use and abuse is two-three times more prevalent for runaways than with the school youths. Runaways' attitudes toward selected illicit behaviors are more tolerant than those of school youths. Intervention programs for runaway/homeless youths should reflect an understanding of the complexity of the psycho-social and behavioral history of the clients which is much different than that of those who are in school.