The Virtual Liver Network (VLN) represents a major research investment by the German Government focusing on work at the “bleeding edge” of Systems Biology and Systems Medicine. This Flagship Programme is tackling one of the major challenges in the life sciences: that is, how to integrate the wealth of data we have acquired post-genome, not just in a mathematical model, but more importantly in a series of models that are linked across scales to represent organ function. As the project is prototyping how to achieve true multi-scale modelling within a single organ and linking this to human physiology, it will be developing tools and protocols that can be applied to other systems, helping to drive forward the application of modelling and simulation to modern medical practice. It is the only programme of its type to our knowledge that bridges investigations from the sub-cellular through to ethically cleared patient and volunteer studies in an integrated workflow. As such, this programme is contributing significantly to the development of a new paradigm in biology and medicine.