Today, one of the main objectives for translational research in radiation oncology throughout the world is to accelerate the application of health care innovations into day-to-day care of the cancer patient. Instead of a one-size-fits-all treatment, “personalized medicine” is presented as a novel strategy that takes into account the individual patient’s characteristics and, based thereupon, strives for better treatment outcomes. Personalization of oncological treatment approaches will define smaller and smaller patient cohorts as candidates for the same treatment, thus requiring large data sets and new approaches of accumulation of clinical knowledge beyond randomized trials. A new computerized electronic health record (EHR) database infrastructure needs to emerge to enable real-time learning from source medical data collected in large volumes across a diverse spectrum of information systems that one can find in modern radiotherapy clinics or research institutes.