Guyton’s original integrative physiology model was a milestone in integrative physiology, combining significant physiological knowledge with an engineering perspective to develop a computational diagrammatic model. It is still used in research and teaching, with a small number of variants on the model also in circulation. However, though new research has added significantly to the knowledge represented by Guyton’s model, and significant advances have been made in computing and simulation software, an accepted common platform to integrate this new knowledge has not emerged. This paper discusses the issues in the selection of a suitable platform, together with a number of current possibilities, and suggests a graphical computing environment for modelling and simulation. Byway of example, a validated version of Guyton’s 1992 model, implemented in the ubiquitous Simulink environment, is presented which provides a hierarchical representation amenable to extension and suitable for teaching and research uses. It is designed to appeal to the biomedical engineer and physiologist alike.