Metabolic inter-organ exchange is a major field of research for improving the treatment of the critically ill. Adapting regional blood flows is the first regulatory step, although the relationships between hypoperfusion and metabolic disorders are matter of controversy. Metabolic steady state results from a vast inter-organ interplay and several nutrients or metabolites are signalling molecules in the regulation of gene transcription. Inter- or intra-organ substrate recycling shares or delays the mandatory need for aerobic ATP synthesis in some conditions. Nitrogen metabolism is highly compartmentalised in an inter-organ co-operation and liver, muscle, kidney and gut are the most important organs. By remodelling the amino acid mixture delivered to peripheral cells after intestinal absorption, the liver plays a determinant role in whole body protein synthesis. Albumin turnover increases after brain injury. Since the location of synthesis is different to that of breakdown this turnover can be viewed as an inter-organ exchange. The metabolic side of pH homeostasis is also an inter-organ exchange mainly shared by liver, kidney and muscle.