Summary Avid mouthing, the propensity of infants to suck objects and put them in their mouths, is a pattern characteristic of the first 2–3 years of life, with its most intensive manifestation occurring during the first year. Although traditional accounts explain infant mouthing as a source of sensual gratification and/or environmental exploration, these proximate hypotheses are inconsistent with the high costs of mouthing, including choking, poisoning, and exposure to pathogens. We propose that mouthing serves to proactively expose the naive gastrointestinal tract to environmental antigens and commensal bacteria while under the sheltering umbrella of breastfeeding. Mouthing functions to accurately calibrate the developing immune system, including antibody production and mucosal immunity, to the local disease ecology. The critical exposure period is not open-ended, as failure to expose the gut to an adequate number of antigens early in life is associated with an increased risk of allergies, asthma, and atopy. Weaning initiates a number of immune changes that may program the neonatal immune system into certain life-long responses.