This paper focuses on past, present, and potential future contributions of ethnographic research to describing and understanding “street cultures” of drug use and the implications these have for informing various interventions. The first section provides an overview of ethnography and drug abuse research. This is followed by a historical perspective on the ethnography of street cultures. Next, the significance of ethnographic drug abuse research is highlighted, with a focus on its methodology. Ethnographic contributions to the development, implementation, and evaluation of interventions are discussed, including ethical issues. Subsequently, the interdisciplinary nature of ethnographic drug abuse research is described. Methodological challenges emerged over time as the definition of street cultures and drug trends shifted. These are illustrated with examples, including the use of prescription drugs, new heroin users, and rural drug and methamphetamine use. The final sections focus on career opportunities for ethnographers and opportunities and barriers for the future. We address training needs for interdisciplinary inquiry, the potential role of ethnographers in prevention and treatment research, and the link to studies on the brain and genetics. The future of ethnographic research on drug use will be influenced by the funding structure. We conclude with a summary of reflections on the past and aspirations for the future.