The Physiome is an umbrella term that refers to human modelling with mathematics and computational methods, accommodating cross-disciplinary science (chemistry, biology, physics) and a breadth of dimensional and temporal scale (sub-cellular to organs, sub-microsecond to tens-of-years). The Virtual Physiological Human is a European initiative that is intended to provide a unifying architecture for the integration and cooperation of multi-scale physiome models, thereby creating a predictive platform for the description of human beings in silico. Unlike the Genome, the challenge of the Physiome may be almost unbounded, as the desire for increased detail imposes a continuing pressure for ever-finer data granularity, and the necessary Information Technology (IT) infrastructure spawns innovations that surpass conventional solutions. It is foreseen that maturing physiome activities will increasingly influence medicine, biomedical research and commercial developments, and the central role of IT highlights the need for a specific and robust IT infrastructure. The European Commission has experience of supporting challenging technical endeavours through its Framework Programmes of research, and in the forthcoming 7th Framework Programme, it will invite researchers from within and outside Europe to unite in seeking solutions to key issues of the Physiome. The Virtual Physiological Human (VPH) investment programme will establish the necessary infrastructure and address the grand technical challenges identified by experts. This paper examines the background to the strategy and the ways in which the programme's structure has been determined.