The ruminant gastrointestinal tract (GIT) faces the challenge of protecting the host from luminal contents and pathogens, while supporting the absorption and metabolism of nutrients for growth and maintenance. The GIT of the calf in early life undergoes some of the most rapid microbial and structural changes documented in nature, and these adaptations in GIT function make the young calf susceptible to GIT diseases and disorders. Despite these challenges, the calf's GIT has a certain degree of plasticity and can sense nutrient supply and respond to bioactive ingredients. Calf GIT research has historically focused on the transition during weaning and characterizing ruminal papillae development using microscopy and digesta metabolite responses. Through the use of new molecular-based approaches, we have recently shown that delaying the age of weaning and providing a step-down weaning protocol is associated with a more gradual shift in ruminal microbiota to a postweaned state. In addition to ruminal adaptations during weaning, nutrient flow to the lower gut changes dramatically during weaning, coinciding with a wide array of structural and microbiological changes. Structural and gene expression changes suggest that the lower gut of the dairy calf undergoes alterations that may reduce barrier function when solid feeds are consumed. More recently, in vivo data revealed that the weaning transition increases total gut permeability of the calf. Interestingly, the lower gut may be able to communicate with the forestomach, meaning that a nutrient can be sensed in the lower gut and cause subsequent adaptations in the forestomach. An improved understanding of how diet, microbiota, and functional ingredients interact to affect growth and barrier function of the intestinal tract would greatly benefit the dairy calf industry. A mechanistic understanding of such adaptations would also aid in the formulation of specific management regimens and provision of functional ingredients required to characterize and enhance gut function in young calves.