Hippocrates was the first to raise awareness of medicine as a science. He asserted the body being a unified whole and emphasized the importance of preventive and predictive medicine, spurring physicians to foster patient collaboration. Recent achievements today have permitted a new approach - ‛P4 medicine’ - Predictive, Preventive, Personalized and Participatory – with the aim of depicting an individual’s health history and molecular profile in determining the best medical intervention in maintaining or restoring wellbeing. This report highlights the link between Hippocrates and P4 Medicine. Moreover, it will discuss how P4 Medicine may help to refine the knowledge of Rare Diseases and define new procedures for faster diagnosis and better therapies. Additionally, it will reveal how Patient advocacy groups and the management of Rare Disease Registries already echo the P4 premises and purposes, underlining the social impact of the new diagnostic and therapeutic protocols.