The development of cardiac models began in 1960 when Denis Noble published his first paper on a model of cardiac cellular electrophysiology [1]. Peter Hunter published his first paper on cardiac electrical modelling in 1975 [2], following his DPhil at Oxford with Derek Bergel on cardiac mechanics. In the following decades the Noble group developed increasingly sophisticated cellular electrophysiology models and the Auckland group (led by Hunter and Smaill) measured and modelled the fibrous-sheet structure of the heart and developed the computational framework for linking cellular physiology to tissue and whole heart function. Over the last 10 years this increasingly collaborative Oxford-Auckland effort has led to the idea of a cardiac ‘physiome’ project, developed under the auspices of the International Union of Physiological Sciences (IUPS) . The Heart Physiome Project is intended to be an internationally collaborative open-source project to provide a public domain framework for computational heart physiology, including the development of modeling standards, computational tools and web-accessible databases of models of structure and function at all spatial scales [3,4,5]. It aims to develop an infrastructure for linking models of biological structure and function across multiple levels of spatial organization and multiple time scales. The levels of biological organization, from genes to the whole organism, includes gene regulatory networks, protein-protein and protein-ligand interactions, protein pathways, integrative cell function, tissue and whole heart structure-function relations. The whole heart models include the spatial distribution of protein expression. The project requires the creation of web-accessible databases of mathematical models of structure and function at spatial scales which encompass nano-scale molecular events to the meter scale of the intact heart and torso, a range of 10⁹, and temporal scales from Brownian motion (microseconds) to a human lifetime (10⁹s), a range of 10¹⁵. Clearly this cannot be represented by one model but rather a hierarchy of models and modeling approaches such as stochastic models of ion channels and receptors for ligand binding calculations, ordinary differential equation lumped cell models, and partial differential equation continuum models at the tissue and organ levels. It also requires the model parameters at one scale to be linked to detailed models of structure and function at a smaller spatial scale – hence the need for “multi-scale modeling”. The long term challenge for the Physiome Project is to build a modeling framework in which the effect of a gene mutation can be modeled all the way from its effect on protein structure and function to how the altered properties of the protein affect a cellular process such as signal transduction, and how the changed properties of that process alter the function of tissues and organs. There will be many other benefits from this integrative framework. Understanding how model parameters are affected by individual variation, by embryological growth, by ageing and by disease, for example, will bring benefits to the design of medical devices, the diagnosis and treatment of disease and the development of new drugs. 1. with Denis Noble and Peter McNaughton (another Oxford kiwi) 2. many others of course have now made major contributions to this collaborative effort, most notably Andrew McCulloch (an Auckland graduate) at UCSD and Peter Kohl and David Paterson at Oxford. A five year grant from the Wellcome Trust, to start in Jan 1st, 2005, will greatly enhance this Oxford-Auckland collaboration and bring in other Oxford cardiac researchers (Richard Vaughan-Jones and Mark Sansom).