The metabolic response to critical illness is an integrated process producing profound changes to multiple systems. The altered metabolism of carbohydrates, lipids, and proteins in critically injured patients, and the crucial role of cytokine mediators such as tumour necrosis factor, interleukins, and interferons are described in detail. A general approach with guidelines for nutritional support is taken. A detailed description of enteral versus parenteral therapy is given, including advantages, disadvantages, contraindications, and complications. The research on specifically enriched amino acid formulations with glutamine, branched-chain amino acids, and arginine solutions is reviewed with emphasis on both theoretical and clinical issues. The role of dietary lipids in the production of specific modulators of immunoresponsiveness and investigations focusing on metabolic modulation relating to nutritional support are summarized.