Individual differences in the behavioral responses to a novel environment have been proposed as a research tool to predict responsiveness to other behavioral tasks, response to certain events and individual vulnerability to nicotine addiction. In rats and mice, novelty seeking (defined as enhanced specific exploration of novel situations) is a complex behavior confirmed by a large body of neurochemical, endocrinological and behavioral data. We review the main standardized procedures employed to measure the novelty seeking trait in rodents and the ontogeny of this behavior throughout the life-span taking into account that novelty seeking can be permanently modified as a consequence of particular early experiences, maternal care, and environmental enrichment. Studies in animal models suggest that individual differences in the sensitivity to nicotine depend on different variables such as basal locomotor activity of the experimental subjects, their response to novel environments (open-field, hole-board) and level of impulsivity. It is concluded that these basic findings contribute to a better understanding of smoking behavior and to the establishment of improved pharmacological treatments if individual differences are borne in mind.