It has been estimated that the gastrointestinal tract accounts for 30% of metabolic and protein synthesis activities of the cow and calf, and thus, plays an important role in animal energetics. Diet and microbiota can positively and negatively affect gut function and the ability to modulate gut function has created an applied interest relevant to improved dairy cow and calf productivity. The mechanisms that govern growth and barrier function of gut tissues have received particular attention, especially with the advancements of molecular based techniques over the past decade. The rumen has been the focal point of dairy cow and calf nutritional physiology research, yet the intestinal tract has received less attention. Three key areas requiring more discovery-based and applied research: (1) early-life intestinal gut barrier function and growth; (2) how the weaning transition affects gut health of rumen and intestine; and (3) gastrointestinal adaptations during the transition to high energy diets in early lactation. Nutrients are not only seen as substrates, but also as signals that can alter gastrointestinal growth and barrier function. Nutrients can act directly, affecting epithelial cell gene expression, and in concert with somatotropic axis hormones, insulin-like growth factor (IGF) and growth hormone where they have been shown to play a pivotal role in gut tissue growth. For example, IGF-1 can mediate other hormones involved in cell growth, such as glucagon-like peptide 2 (GLP-2), whereas, intestinal GLP-2 is secreted upon nutrient ingestion causing a stimulation of intestinal growth. The latest research suggests that total-tract barrier function in calves and cows in early life, at weaning and in early lactation is compromised. A major factor for gut health is maintaining proper gastrointestinal barrier function, which is highly influenced by the presence of metabolites (butyrate) and resident microbiota and/or direct fed microbials within the gut. In the first studies that investigated barrier function in cows and calves, it was determined that the expression of genes encoding mucin and tight junction regulating proteins, such as claudins, occludins and desmosomal cadherins, are regulated by diet. Additionally, recent evidence suggests that the upper and lower gut can communicate, but the exact mechanisms of gastrointestinal cross-talk have not been studied in detail. A deeper understanding of how diet and microbiota can affect growth and barrier function of the intestinal tract would provide knowledge of what specific management regimens could effectively impact gut function.