This paper presents a brief overview of several components of tobacco addiction, including: 1) the epidemiology of smoking in the United States and elsewhere around the world; 2) implications of the pharmacogenetic study of nicotine metabolism for understanding tobacco addiction and its treatment; 3) the use of the twin design as an example of one strategy to understand the contribution of genetic and environmental factors to the pharmacokinetics of nicotine metabolism; 4) results from recent genomic studies of tobacco addiction in adults; and 5) a discussion of progress (past and future) toward the development of a comprehensive understanding of the pharmacogenetics of tobacco addiction and its treatment.