Decades of epidemiological research have established that breastfeeding is associated with a modest reduction in risk of later overweight and obesity. However, no systematic effort has been made to delineate the mechanisms that may explain this association. This review summarizes evidence from a variety of disciplines to understand the potential mechanisms underlying this association. One possibility is that this association is spurious and that confounding factors fully or partially explain this association. Additionally, breastfeeding could confer protection by: encouraging the infant's emerging capabilities of self-regulation of intake; reducing problematic feeding behaviors on the part of caregivers that interfere with the infant's self-regulation of intake; and providing bioactive factors that regulate energy intake, energy expenditure, and cellular chemistry. These three protective effects may promote slower growth and lower body fat levels in breastfed infants, which reduce risk of overweight and obesity later in life.