This paper reviews recent research on adolescent smoking initiation and youth tobacco prevention and control strategies. Gender, ethnicity, family factors, and genetics are associated with smoking initiation and adolescent tobacco use. Evidence indicates that comprehensive tobacco control programs are an effective strategy for reducing adolescent smoking, and even modest gains from prevention and cessation efforts could lead to substantial reductions in the morbidity and mortality costs of smoking. Clinicians have an important role in prevention and treatment of tobacco use in adolescents, and the rate of delivery of clinical preventive services in this area should be increased. Consequently, clinicians working with adolescents should be familiar with established guidelines regarding tobacco use prevention and treatment and use general outpatient office visits as an important opportunity to prevent tobacco use.