Active and passive exposure to tobacco smoke during pregnancy and infancy is the most serious and preventable cause of adverse maternal, fetal, and infant outcomes in the United States. The multiple risks of tobacco exposure to mothers and infants are definitive, and the clinical and economic benefits of cessation have been documented. This article provides a synopsis of the state of the science and art in this specialized area and reviews the evidence for validity of patient assessment methods and the effectiveness of smoking cessation/reduction treatments for pregnant women. A synthesis of 4 topics is presented: (1) the validity of patient reports of smoking status and recent trends during pregnancy and postpartum; (2) definition of "Best Practice" smoking cessation methods for pregnant women; (3) the effect of dissemination of effective clinical practice methods among the 800,000+ pregnant US smokers each year; and (4) the evidence for the cost-benefit of improved maternal and infant outcomes from cessation.