Can one bottle of formula (or more) really affect a newborn infant or derail breastfeeding? While it may sound harmless and helpful, bottles of infant formula given to newborn breastfeeding infants have been shown to interfere with the successful establishment of breastfeeding, reduce both the exclusivity and duration of breastfeeding, and permanently alter the infant gut microbiome. One bottle of formula per day for the first week of life is enough to shift the gut microbiome toward proinflammatory taxa, a condition where gut inflammation becomes the precursor to both acute and chronic diseases and conditions such as autoimmune diseases and obesity. Yet, some infants and maternal situations may require medically indicated supplementation, so how can unwanted side effects of infant formula be reduced or prevented? This presentation will explore the side effects of just one bottle, discuss scenarios where a supplement may be needed, and present approaches and alternatives to the high rate of formula supplementation seen in some hospitals and in the early days following birth.