Over the last 10 years, 'Systems Biology' has focused on the integration of biology and medicine with information technology and computation. The current challenge is to use the discoveries of the last 20 years, such as genomics and proteomics, to develop targeted therapeutical strategies. These strategies are the result of understanding the aetiologies of complex diseases. Scientists predict the data will make personalized medicine rapidly available. However, the data need to be considered as a highly complex system comprising multiple inputs and feedback mechanisms. Translational medicine requires the functional and conceptual linkage of genetics to proteins, proteins to cells, cells to organs, organs to systems and systems to the organism. To help understand the complex integration of these systems, a mathematical model of the entire human body, which accurately links the functioning of all organs and systems together, could provide a framework for the development and testing of new hypotheses that will be important in clinical outcomes. There are several efforts to develop a 'Human Physiome', with the strengths and weaknesses of each being presented here. The development of a 'Human Model', with verification, documentation and validation of the underlying and integrative responses, is essential to provide a usable environment. Future development of a 'Human Model' requires integrative physiologists working in collaboration with other scientists, who have expertise in all areas of human biology, to develop the most accurate and usable human model.