Much cancer and most diabetes would be avoided if people did not smoke, moderated alcohol use, consumed less food, and became physically active. Achieving such change in these behaviors across populations would also reduce much of the gaps in health and life expectancy between the rich and the poor. In this chapter we first describe attempts to change these four aspects of behavior over the last century, focusing on the United States and the United Kingdom. We then elaborate on one particular and recent set of interventions, altering “choice architecture” or micro-environments, that can change behavior, often without conscious awareness. We argue that these show greater potential for achieving change across populations than hitherto predominant approaches that are delivered individually and/or rely on information and persuasion. We outline the conceptual and empirical research needed to estimate the contribution choice architecture interventions could make to changing behavior in populations at the scale and pattern needed to prevent noncommunicable chronic diseases in the poorest as well as the richest. In addition to this scientific challenge, we note the need to address the political challenge that stems from free market economies built on overconsumption, including what can be considered the main vectors of noncommunicable disease in the 21st Century: tobacco, alcohol, processed foods, and transport powered by fossil fuels.