Medicine is undergoing a revolution that is transforming the nature of healthcare from reactive to preventive. The changes are catalyzed by a new systems approach to disease which focuses on integrated diagnosis, treatment and prevention of disease in individuals. This will replace our current mode of medicine over the coming years with a personalized predictive treatment. While the goal is clear, the path is fraught with challenges. P-medicine brings together international leaders in their fields to create an infrastructure that will facilitate this translation from current practice to personalized medicine. In achieving this objective p-medicine has formulated a coherent, integrated work plan for the design, development, integration and validation of technologically challenging areas of today. Our emphasis is on formulating an open, modular framework of tools and services, so that p-medicine can be adopted gradually, including efficient secure sharing and handling of large personalized data sets, enabling demanding Virtual Physiological Human (VPH) multi-scale simulations (in silico oncology), building standards-compliant tools and models for VPH research, drawing on the VPH Toolkit and providing tools for large-scale, privacy-preserving data and literature mining, a key component of VPH research. We will ensure that privacy, non-discrimination, and access policies are aligned to maximize protection of and benefit to patients. The p-medicine tools and technologies will be validated within the concrete setting of advanced clinical research. Pilot cancer trials have been selected based on clear research objectives, emphasising the need to integrate multilevel datasets, in the domains of Wilms tumour, breast cancer and leukaemia. To sustain a self-supporting infrastructure realistic use cases will be built that will demonstrate tangible results for clinicians. The project is clinically driven and promotes the principle of open source and open standards.