Experimentally based models of the heart have been developed since 1960, starting with the discovery and modelling of potassium channels. The early models were based on extensions of the Hodgkin-Huxley nerve impulse equations. The first models including calcium balance and signalling were made in the 1980s and have now reached a high degree of physiological detail. During the 1990s these cell models have been incorporated into anatomically detailed tissue and organ models to create the first virtual organ, the Virtual Heart. With over 40 years of interaction between simulation and experiment, the models are now sufficiently refined to begin to be of use in drug development.