Noncommunicable diseases (NCDs), including cancer, are responsible for almost 70% of all deaths worldwide. Tobacco use is a risk factor common to most NCDs. This article discusses tobacco control policies and highlights major achievements and open challenges to reduce smoking prevalence and attributable morbidity and mortality in the 21st century. The introduction of the WHO Framework Convention on Tobacco Control in 2005 has been a key achievement in the field and has already facilitated a drop in both smoking prevalence and exposure to secondhand smoke. Indicatively, the size of the worldwide population benefiting from at least one cost-effective tobacco control policy has quadrupled since 2007. In addition, plain cigarette packaging has been successfully introduced as a tobacco control policy, surmounting efforts of the tobacco industry to challenge this based on trade and investment law. Nevertheless, tobacco control still faces major challenges. Smoking prevalence needs to be further reduced in a rather expedited manner. Smoke-free environments should be extended, and the use of plain tobacco packaging with large pictorial health warnings for all tobacco products should be further promoted in some parts of the world. Some of these measures will require prompt determination and diligence. For example, bold political decisions are needed to significantly increase real prices of tobacco products through excise taxes, ban added ingredients that are currently used to increase the attractiveness of tobacco products and ban the tobacco industry's corporate social responsibility initiatives. Finally, the debate on harm reduction strategies for tobacco control still needs to be resolved.