Medium-chain fatty acids, branched-chain amino acids, and glutamine have been shown to be of clinical benefit and should be in common use in the near future. Short-chain fatty acids still are under investigation. Albumin, vitamins E and C, arginine, glutamine, and omega-3 fatty acids show great promise as pharmacologic agents to manipulate the stress response. Nucleotides remain investigational. CONTENTS SUMMARY: The application of some new nutritional substrates for use in critically ill patients, both as caloric sources and as pharmacologic agents, are reviewed.