Breast is best. However, it has never been the only option. There was, and will always be, a need for human milk substitutes, no matter how successful the promotion of breastfeeding. Currently available infant formulas do not raise safety concerns regarding growth and adverse effects. However, there are differences between breastfed and formula-fed infants with respect to short- and long-term outcomes. Thus, opportunities for further improvement of infant formulas exist. Considering the role the gut microbiota plays in health and diseases, efforts are being made to refine the composition of infant formulas to resemble the functionality of human milk. This includes the addition of biotics such as probiotics, prebiotics, synbiotics, and postbiotics to infant formulas.