Emerging technological advances in genetics and neuroscience have spawned innovative or elaborated conceptual models in the field of addiction science, as well as contributed to the mushrooming of new knowledge. By addictions, reference is made to chronic, often relapsing disorders typified by obsession, compulsion, or physical or psychological dependence. In this article it is proposed that a multilevel developmental contextual approach to substance use and addictions provides a useful framework for integrating existing studies across disciplines and serving as a generative guide to intriguing novel research questions. The multilevel developmental contextual approach emphasizes multiple factor influences on substance use and addiction, the conjoint influence of variables from different levels of analysis (e.g., genetic, biochemical, physiological, cognitive, social, neighborhood, societal), and dynamic, probabilistic behavior-outcome relations (i.e., the occurrence as well as the nature of expression of substance problems and addiction depend on a range of emerging, interactive factors that may vary across individuals and across time). The approach is illustrated with a long-term prospective study of predictors of binge drinking from adolescence to young adulthood and a description of the role of brain processes and mechanisms involved in the development and expression of alcohol use during adolescence.