The suspicion that the use of tobacco adversely affects health existed for some time before a case-control study appeared in 1950 of 684 cases of lung cancer strongly associated with cigarette smoking. This paper, a brief history, describes the background of the 1950 landmark study as well as other pertinent epidemiologic and experimental studies of the 1950s and 1960s. This body of research provided evidence for the causative association between tobacco use and lung cancer and other chronic diseases such as several other types of cancer and coronary heart disease. Despite this body of evidence, support from scientists, health professionals, and government officials on the issue of smoking and health came slowly. The scientific application of this discovery to prevent tobacco-linked diseases continues to be far more difficult than the discoveries themselves. Thus, although the low-yield cigarette has provided some assistance to smokers, smoking prevention is far more important, and greater efforts are needed to achieve cessation, particularly among women and minority groups. Beyond this approach, efforts to prevent children and young people from beginning to smoke should stress State-mandated school health education beginning in the earliest grades. The Know Your Body School Education Program, which includes an annual screening with the results entered into a personalized Health Passport starting in first grade, has demonstrated reductions in onset of smoking as well as improved health behavior in nutrition. To further reduce tobacco use, cancer prevention units staffed by health educators, behavioral scientists, and epidemiologists should practice prevention on a communitywide basis. The prevention of diseases as the ultimate aim of medicine and science can be demonstrated by the smoking and health issue that establishes that the prevention of many cancers is attainable.