Tobacco use and exposure to tobacco smoke remain major but avoidable causes of premature mortality and disease worldwide. Although the age-standardized prevalence of daily smoking has declined for both men and women in many countries, the number of smokers continues to increase because of global population growth. Although cigarettes are the most commonly used tobacco product, the tobacco epidemic has become tremendously complex with the emergence and popularity of alternative products such as waterpipes and electronic cigarettes (also known as e-cigarettes). Exposure sciences play a major role in characterizing the tobacco epidemic as well as in the promotion, enactment, and implementation of tobacco control initiatives including legislation and voluntary measures in countries worldwide. We reviewed several studies in Latin America and other regions, showing how high-quality exposure assessment has contributed to smoke-free policies. Although there are many toxicants in tobacco products, metals could be playing an important role in tobacco-related disease. Tobacco plants accumulate cadmium and lead from soil. In e-cigarettes, a metallic coil heats the e-liquid to produce the aerosol that is inhaled by the vaper, and studies have found high aerosol levels of nickel, chromium, lead, and zinc. Despite many tobacco control successes, including the enactment of the Framework Convention on Tobacco Control, which has been ratified by 181 countries, tobacco control faces many challenges globally. Given the continuing increase in the number of smokers worldwide and the rapid emergence of new tobacco products, additional creative efforts are needed to achieve a smoke-free world, help smokers to quit, and protect youth from initiating tobacco use.