Approximately three-quarters of adult tobacco users report that their first tobacco use occurred between ages 11 and 17, while many adults who do not regularly use tobacco report that they experimented with it as adolescents. Surprisingly little is known about the effects of these initial tobacco use episodes and their influence on adult tobacco use patterns. In particular, understanding the role that nicotine plays in these early tobacco use experiences may be important in understanding the development of regular tobacco use and concomitant nicotine dependence. One goal of this review is to summarize current knowledge regarding the effects of initial tobacco use episodes in adolescents and to discuss nicotine exposure in initial tobacco use episodes. Another goal is to outline a research agenda designed to learn more about initial tobacco use episodes and the effects of nicotine in children. An ethical rationale and some potential methods for this research agenda are presented.