This Special Issue of Preventive Medicine (PM) focuses on behavior change, health, and health disparities, topics of fundamental importance to improving population health in the U.S. and other industrialized countries. While the U.S. health care system and those of other industrialized countries were developed to manage infectious disease and acute illnesses, it is chronic health conditions that most need to be understood and managed in the 21st century. The evidence is clear that personal behavior patterns like cigarette smoking and physical inactivity/obesity are critically important proximal causes of chronic disease (cardiovascular disease, site-specific cancers, type-2 diabetes) and as such behavior change will need to be a key component of their management. As the outstanding contributions to this Special Issue illustrate, substantial headway is being made in advancing knowledge including developing effective prevention and treatment strategies, with cigarette smoking being an excellent example that change is possible. That said, cigarette smoking continues to be responsible for approximately 480,000 premature deaths annually in the U.S. alone and 5 million globally. So more needs to be done, especially in economically disadvantaged populations. The same certainly applies to the challenges of the obesity epidemic, which of course is a more recent problem and understandably efforts to curtail it are in earlier stages of development.