This chapter reviews the array of methods used in contemporary research on population-level research on substance use and its consequences. We argue that there are critical questions that can best – or in some cases, only – be addressed at the level of a population. We then describe the major categories of data collection methods used in population research, including surveys, ecological momentary assessment, administrative data, audit methods, and unobtrusive assessment of substance use. Two categories of measures are then discussed: measures of an individual’s use of substances and related problems and measures of harm to others caused by one’s use. We then review factors that may be considered causes or correlates of substance use and consequences, including both individual and environmental factors. We close with a few thoughts on the accumulation of knowledge and its translation to policy and practice.