The goal of the present study was to determine the relationship between substance use, drug selling, and lethal violence in adolescent male homicide offenders and their victims. The study employed a retrospective review of criminal justice databases and medical examiner records for murders committed by 25 adolescent males incarcerated in the Commonwealth of Virginia juvenile correctional centers from February 1992 to July 1996. The perpetrator sample was 84% African American and 16% white. The average age at the time of the offense was 15.0 years (range = 13.0 to 17.7 years). The victims were 84% male, 60% African American and 32% white. The median victim age was 28.0 years (mean = 34.8, range = 17 months to 75 years). The results indicated that 52% of the murders were committed by juveniles with identified involvement in drug selling, and 28% of the murders were drug-related. Toxicology results indicated recent drug or alcohol use in 27% of the victims; while 74% of the perpetrators reported substance use, 35% indicating daily use. Using discriminant analysis, it was possible to accurately classify 86% of the drug-related murders with the variables of recent victim drug use and perpetrator substance use history. The results indicated that adolescent males involved in the sale and distribution of illegal drugs comprised a significant percentage of those incarcerated for murder. Recent victim drug use and perpetrator substance use may be important variables in identifying drug-related juvenile homicides. These results underscore the link between substance use, drug selling, and lethal violence.