After one of the most intense public health campaigns in history, now over 40 years old, about 45 million Americans continue to smoke. Each year 400,000 smokers die from smoking-related diseases because they are unable - or at least unwilling - to achieve cessation through complete nicotine and tobacco abstinence. This presentation reviews the substantial scientific evidence for tobacco harm reduction, which involves the replacement of cigarettes with alternative sources of nicotine, including modern smokeless tobacco (ST) products. It summarizes the epidemiologic evidence that ST use confers only 0.1°/ to 10% of the risks of smoking with respect to all smoking-related diseases, including oral and other cancers and cardiovascular diseases. The presentation also describes evidence that ST has served as an effective substitute for cigarettes among Swedish men, who consequently have among the lowest smoking-related rnortality rates in the developed world. The presentation concludes by discussing the growing interest in tobacco harm reduction among tobacco research and policy experts from around the world.