Urbanization is probably the single most important demographic shift world-wide throughout the past and the new century and represents a sentinel change from how most of the world's population has lived for the past several thousand years. As urban living becomes the predominant social context for the majority of the world's population, the very ubiquity of urban living promises to shape health directly and to indirectly affect what we typically consider risk factors or determinants of population health. Although a growing body of research is exploring how characteristics of the urban environment may be associated with health (e.g. depression) and risk behaviours (e.g. exercise patterns), relatively little research has systematically assessed how the urban environment may affect drug use and misuse. In this paper we will propose a conceptual framework for considering how different characteristics of the urban environment (e.g. collective efficacy, the built environment) may be associated with drug use and misuse, summarize the existing empiric literature that substantiates elements of this framework, and identify potential directions for future research.