Individual differences in susceptibility to nicotine addiction, the likelihood of successful smoking cessation, and the development of adverse health effects of smoking are well recognized. The basis for these individual differences is as yet unknown. This chapter examines individual differences in the metabolism and kinetics of nicotine as a possible factor. Rare individuals appear to be deficient metabolizers of nicotine. Individual differences are described both in the pattern and rates of nicotine metabolism. Ethnic differences in cotinine metabolism have also been observed. However, the enzymes responsible for nicotine metabolism and their genetic regulation have not been fully characterized. Understanding the basis for individual differences in nicotine kinetics and metabolism, and linking these differences to pharmacodynamic studies, may provide important clues for the prevention and treatment of nicotine and possibly other drug addictions.