The development of both technology, biological, and clinical knowledge leads to remarkable changes of scientific research methodology, including the clinical research. Major changes deal with the pragmatic approach of trial designs, an explosive diffusion of observational research which is becoming a usual component of clinical practice, and an active modelling of new research design. Moreover, a new healthcare landscape could be generated from the information technology routinely used to collect clinical data in huge databases, the management and the analytic methodology of big data, and the development of biological sensors compatible with the daily life delivering signals remotely forwardable to central databases. Precision medicine and individualized medicine seem to be the big novelties of the coming years, guiding to a shared pattern of patient/physician relationship. In healthcare, a huge business related mainly, but not exclusively, to the implementation of information technology is growing. This development will favor radical changes in the health systems, also reshaping the clinical activity. A new governance of the research strategies is needed and the application of the results should be based on shared ethical foundations. This new evolving profile of medical research and practice is discussed in this paper.