On November 10, 2015, the U.S. Food and Drug Administration approved, for the first time, the sale of smokeless tobacco products authorized under the new premarket tobacco application pathway. This Food and Drug Administration regulatory decision draws attention to the growing worldwide use of smokeless tobacco products in general. Use of these tobacco products is particularly popular in low- and middle-income countries of Asia. Due to aggressive and strategic marketing to children, young adults, and current smokers, rates of smokeless tobacco use in men of all ages are on the rise in United States and elsewhere. The tobacco industry also continues to market these products to current cigarette smokers for use in the growing number of “smoke-free environments.” Smokeless tobacco products are associated with cancers of the upper aerodigestive tract, particularly the oral cavity, esophagus, and pancreas; cardiovascular diseases; small-for-gestational-age infants; premature births; increased risk of apnea; and stillbirth. There is no convincing evidence regarding the efficacy of smokeless tobacco, including snus, to promote smoking cessation. Rather, studies from Europe and the United States demonstrate that smokeless tobacco use may facilitate regular cigarette smoking by acting as a gateway drug, especially for children. Caution is warranted before proposing smokeless tobacco as a harm-reduction strategy, in part because of the potential for further promoting smokeless tobacco in low- and middle-income countries where use is already widespread. Continued vigilance through comprehensive surveillance is warranted. We strongly recommend the use of graphic warning labels as a “no regrets” strategy for all smokeless tobacco products marketed globally.