The purposes of this article are to introduce a formal definition of nipple confusion and to propose various hypotheses concerning its cause. The term nipple confusion refers to an infant's difficulty in achieving the correct oral configuration, latching technique, and suckling pattern necessary for successful breast-feeding after bottle feeding or other exposure to an artificial nipple. Many early breast-feeding failures are attributed to nipple confusion, although scientific data are lacking to document its prevalence, the mechanisms involved, or various factors that predispose an infant to this phenomenon. Two classifications of nipple confusion are recommended to distinguish the impact of artificial nipples during the newborn period from their influence after breast-feeding is well established. Maternal and infant risk factors making an infant more susceptible to nipple confusion are discussed. Future studies are planned to help elucidate the nature of nipple confusion and identify the circumstances under which infants are most vulnerable to this phenomenon. Meanwhile, it would seem prudent for clinicians to identify newborns at risk for nipple confusion and to minimize the use of bottle feedings in such babies. Medically indicated supplements in the early days of life could be provided by alternative methods, such as cup, spoon, or dropper feeding, until breast-feeding can be established.