Intensive insulin control has demonstrated several improved outcomes among patients requiring intensive care, ranging from reduced need for dialysis to reduced patient mortality by up to 45 %. To ensure effective insulin control, physiologically relevant three-compartment insulin kinetics models are necessary to understand the endogenous insulin component in controlling the patient. Due to difficulty in identifying these models uniquely, simplified two-compartment models are often used. This book suggests a more physiologically accurate three-compartment model, based on a clinically validated two-compartment model. The suggested model is implemented and validated on high-density clinical data. Validation shows insulin, C-peptide, and glucose concentrations closer to the measured data than the previously validated study, suggesting an accurate estimate of endogenous insulin secretion and kinetics in the model. This book presents an accurate method and tool for use in critical care and other research, and should be especially useful to people interested in the areas of insulin modelling and general model-based medical decision support.