Tobacco use is recognized as the most significant cause of preventable morbidity and mortality. In recent years health professionals have shifted emphasis from treating adult smokers to preventing smoking among children. This has prompted a number of studies of the determinants of smoking behavior among adolescents. Although some recent research has associated low self-esteem with smoking, other work challenges the relationship between self-esteem and health behavior. This study examines the relationship between adolescent self-esteem and smoking among a large cohort (N = 3,567) of adolescents who were surveyed between the 6th and 10th grades. Findings suggest that self-esteem may be a factor in the smoking behavior of female adolescents in grades 6-8, but not for males in any grade. This suggests that females may have different motivations to initiate and maintain the smoking habit.