In this short review, our current understanding of key aspects of the catabolic response are presented in the context of the seminal contributions of Sir David Cuthbertson. Studies have confirmed that an increase in resting energy expenditure occurs in almost all forms of critical illness and injury. However, meeting the resulting increase in caloric requirement is not an insurmountable problem. The primary focus of nutritional support should be the net loss of body protein. Increased intake of dietary protein may ameliorate, but usually will not entirely reverse, the accelerated loss of body protein because of anabolic resistance. Anabolic resistance is due, at least in part, to impaired inward transport efficiency of amino acids from blood into muscle. Simultaneous consumption of excess non-protein calories in an anabolic resistant state provides minimal additional benefit, and may cause potentially adverse effects, including accumulation of liver fat and excess production of carbon dioxide. Because of the limited effectiveness of dietary protein and non-protein caloric intake, it is likely that traditional nutritional support alone will not reverse the net loss of body protein in the catabolic state. The reversal of the catabolic response can only be accomplished in many patients by combining reasonable nutritional support with appropriate metabolic control. Metabolic control may be achieved with the use of a number of pharmacological approaches, including propranolol, insulin or testosterone. Regardless of the approach, ensuring an adequate availability of dietary essential amino acids is necessary for pharmacologic therapy to result in an increased rate of protein synthesis.