Clinical decision making is ideally founded on evidence of efficacy derived from well-designed randomized clinical trials. In reality, such evidence is rarely available to the surgeon caring for the patient with multiple trauma or who is critically ill, and complex management decisions must be made by less rigorous, more subjective means. An understanding of the normal biologic state and its alterations during disease has long been a fundamental component of medical education. Although such an understanding does not provide practitioners with grounds for assuming therapeutic efficacy in a particular patient, it does shape their perception of the important principles that guide the decision-making process. In contrast to evidence-based medicine--the making of therapeutic decisions through the systematic synthesis of results of clinical trials--a knowledge of pathobiology supports a complementary approach that the authors term "inference-based medicine"--the use of insights from studies in basic biology to establish principles that guide the practitioners' approach to groups of patients. The impact of a relatively new area of biologic investigation into the effects of the gut flora on systemic homeostasis, and the perturbations of this process in trauma and critical illness are reviewed. Re-emergence of the "gut hypothesis" has had a relatively modest effect if measured by the introduction of promising new forms of specific therapy. However, these investigations have resulted in a fundamental paradigm shift in two important areas in the practice of trauma and critical care surgery: the use of antimicrobial agents and the route of nutritional support.