Translational medicine has been fairly unsuccessful in translating innovation from the lab towards the clinics and back again. Many reasons account for the failure leading to a massive waste in life science research and the steep rise in costs of drug development and a failing pipeline from academia towards industry. The development of biomarkers suffers from similar problems. Despite all high hopes of advances such gene sequencing and multiplex technologies, translation from ‘big data’ into tangible therapies has been fairly unsuccessful with a few notable exceptions. Therefore, in order to truly advance translational medicine we need to examine carefully the root causes of the current problems and set out a completely new course, based on a paradigm shift in thinking about the way we collaborate and perform translational medicine.