OBJECTIVE Recognition that the gastrointestinal tract is a key element of the immune system has led to a greater interest in understanding its role as a central figure in host defenses. Biologic systems that are perturbed by any destabilizing stimulus are known to respond by adaptive strategies in an attempt to maintain or return to global homeostasis. In critically ill patients, the gut has previously been described as a promoter of progression to sepsis and multi-organ failure. However, with better understanding of gastrointestinal tract mucosal immunity, we are now provided with a new arsenal to combat nosocomial infection and significantly impact return to health. RESULTS In this review we focus on five key topics in the rapidly expanding landscape of knowledge on the gastrointestinal tract in the critical care setting. These include a discussion of probiotic therapy, now the new frontier of immuno-nutrition, the concept of ischemia/reperfusion injury and changes in gut permeability, anti-oxidant and micronutrient therapy, blood glucose regulation, and enhancement of gut motility, all in the intensive care setting. CONCLUSIONS Ongoing research in nutritional support in both normal and pathologic gastrointestinal function and response to injury has opened the door to several new opportunities for enhancing rapid recovery in critical care.