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The ability to collect, store and analyze massive amounts of molecular and clinical data is fundamentally transforming the scientific method and its application in translational medicine. Collecting observations has always been a prerequisite for discovery, and great leaps in scientific understanding are accompanied by an expansion of this ability. Particle physics, astronomy and climate science, for example, have all greatly benefited from the development of new technologies enabling the collection of larger and more diverse data. Unlike medicine, however, each of these fields also has a mature theoretical framework on which new data can be evaluated and incorporated—to say it another way, there are no ‘first principals’ from which a healthy human could be analytically derived. The worry, and it is a valid concern, is that, without a strong theoretical underpinning, the inundation of data will cause medical research to devolve into a haphazard enterprise without discipline or rigor. The Age of Big Data harbors tremendous opportunity for biomedical advances, but will also be treacherous and demanding on future scientists.