“Gut health”, a catch-phrase used loosely across the animal nutrition industry, lacks a clear and simplistic definition, due to the complexity of the gastrointestinal tract in relation to physiological systems. The key to understanding the relationship between gastrointestinal function and animal health is a fundamental understanding of the integral role gastrointestinal organs play in regulating homeostatic functions, especially as related to protection from pathogens and immune tolerance. Contributing to the complexity of putting gastrointestinal health into tangible and descriptive terms is the dynamic relationship between dietary components and livestock management on the mucosal immune system, intestinal microflora, epithelial integrity, utilization of nutrients, and mucosal function. Further, recent literature reports that stress events impact short- and long-term functionality of gastrointestinal integrity and are linked to a depression in growth performance, thus showing the gut has a memory to stress events. Accurate measurement of gastrointestinal function is critical to valuation of health-promoting benefits of nutritional and management strategies. Unfortunately, assessment of the aforementioned strategies cannot always be conducted under commercial settings, therefore the strategic use of in-vitro and in-vivo research models is critical. Recent developments in the use of intestinal cell culture models, such as the secondary porcine cell culture line IPEC-J2 and porcine gut enteroids show promise in understanding the relationship between nutritional strategies, intestinal stressors, and epithelial integrity. Further, the use of in-vivo research models show that common in-field stress events can be partially mimicked to study gastrointestinal function. Additionally, assessment of the microbiome, metabolomics, and mucosal immune function can provide another piece of the puzzle in understanding gastrointestinal dynamics. However, in-vitro experimental models, molecular, and microbial measurements should be accompanied with classical systemic measurements, such as nutrient digestibility and utilization and growth performance, to allow for practical interpretation of results. Understanding “gut health” requires a fundamental understanding of the intestinal epithelium, the immune system, the intestinal microbiome, and the crosstalk that exists between these components. Further, measurement of “gut health” requires utilization of in-vitro and in-vivo research models coupled with novel and classical measurements.