Smoking continues to be the leading cause of preventable death in the United States, responsible for about one of every five deaths. Worldwide, 1 billion men and 250 million women use tobacco products. Nicotine, the primary psychoactive and addictive chemical in tobacco, drives tobacco use, leading to serious health consequences including the death of half all long-term smokers. Given the burden smoking-related mortality/morbidity poses worldwide, policies and treatment are necessary. This article reviews tobacco use, nicotine addiction pharmacology/biochemistry, health consequences of smoking, including a focus on vulnerable groups, and newer topics in the areas of smoking, tobacco, and nicotine delivery.