Individual variation in nicotine metabolism may play a role in a person's level of smoking, as well as in the transition from initiation to maintenance of a smoking behavior pattern. Since there is a paucity of research on nicotine metabolism in youth that smoke, a brief review of salient aspects of nicotine metabolism in adults provides a basis from which to extrapolate. We do know that factors influencing the rate of nicotine metabolism include differences in nicotine intake and absorption, inhalation patterns, genetic polymorphisms of pertinent enzymes, as well as daily activities such as meal consumption. Variability is illustrated with differences in cotinine levels identified in African-American and Caucasian women and in menthol and nonmenthol smokers. There are a number of areas where more information to improve understanding the initiation and maintenance of smoking behavior is needed. Characterization of nicotine metabolism and smoking topography in youth from multiple ethnic groups who are engaged in smoking initiation is currently lacking. Important measures of smoke constituent exposure such as carbon monoxide, nicotine and cotinine, as well as puff volume and duration and respiratory movements should be addressed. While there are numerous factors that impact initiation and maintenance of smoking behavior, nicotine metabolism may represent one important aspect.