This paper traces the history of noncommunicable disease public health research and programming at the World Health Organization. Specifically, it investigates the origins of the now pervasive 4 × 4 framework focusing on four sets of diseases (cardiovascular diseases, diabetes, chronic respiratory diseases, and cancers) caused by four behavioral risk factors (tobacco use, harmful use of alcohol, unhealthy diets, and physical inactivity). We have found that the 4 × 4 framework developed as a generalization from strategies to control epidemics of cardiovascular disease and stroke in high-income countries during the second half of the twentieth century. These strategies, which were narrowly focused on interventions to address behavioral "lifestyle" risk factors as well as pharmacotherapy for physiologic risk factors, were ultimately packaged as an integrated approach initially in high-income countries and subsequently extended to low- and middle-income countries, where they have failed to address much of the burden among very poor populations.