The paper introduces a structured approach to transforming healthcare towards personalized, preventive, predictive, participative precision (P5) medicine. It highlights the promising methodological paradigm changes, accompanied by related organizational and technological ones. In the latter context, the deployment of artificial intelligence and autonomous systems is crucial beside miniaturization and mobility. Beside their opportunities, those advanced technologies also bear risks to be managed. Beside the relationships between technology and human actors, the behavior of intelligent and autonomous systems from a humanistic and ethical perspective is in the center of considerations. The different existing approaches for guaranteeing the intended properties are presented and compared for deriving a common set of necessary principles to be met for P5 medicine.