The Infrastructure for Systems Biology in Europe (ISBE) programme comprises an infrastructure that is designed to meet the needs of European systems biology, in terms of development, applications and training. In order to address this requirement, we are proposing a distributed, interconnected infrastructure which primarily comprises three types of centres: Data Integration Centres (DICs), and systems biology dedicated Data Generation Centres (DGCs), and Data Stewardship Centres (DSCs). DICs are research centres that apply and develop expertise in model-driven data integration and make this expertise available to the community. DGCs are technology-based centres that make available a wide range of high, medium and low throughput technologies that are essential for the acquisition of quantitative datasets under standardised conditions. DSCs are centres that are responsible for data processing, curation and analysis – they store data, models and simulations. Each type of centre will be functionally different, but organisationally similar. Within participating universities and other organisations across Europe there will be foci of expertise and facilities which fit the requirements for a DIC, DGC or DSC. Such foci will be evaluated and then designated as local centres of a particular type. Each focus will then form a component of a particular type of DIC, DGC or DSC centre. ISBE centres may be single institutions or can be distributed. Large institutions, such as leading universities, may well contribute facilities and expertise across different types of centres. A particular distributed centre may focus on an area of Systems Biology; for example, a model organism, a disease, or, alternatively an area such as biotechnology, ecology or green biology. Importantly, the ISBE will include technological expertise; for example, stochastic computation, algorithmic modelling, multi-scale modelling integration of diverse high-and low-throughput datasets.