Human milk provides the nursing infant with molecules critical to infant development, homeostasis, and health. A fraction of these molecules are partially or fully indigestible and thus delivered intact to the infant colon. This includes human milk oligosaccharides (HMOs) and nitrogenous molecules that potentially provide functions beyond their intrinsic nutritive value. Accordingly, these human milk molecules interact with gut microbes to modulate the emergent physiology of the gut microbiome. Human milk non-protein nitrogen (NPN) is relatively poorly characterized, in particular their interactions with commensal microbiota. The genomics and molecular microbiology underlying reciprocal interactions between beneficial bifidobacterial populations and human milk molecules will be presented with an emphasis on HMOs and NPN.