Energy and protein metabolism in septic and trauma patients has been extensively studied over the past 30 years. Despite this, a number of inconsistencies are present in the literature and it is difficult to formulate a clear global picture of this complex series of metabolic events. Conclusions from human studies have often been hampered by the utilization of small numbers of patients, and data from animal models of sepsis or trauma are often difficult to interpret. Over the past 5 years, the authors have performed a series of isotopic infusions in normal volunteers, and in patients with either sepsis or trauma, in order to gain a clearer understanding of energy and protein metabolism in severely stressed patients. This review summarizes the findings.