AbstractBig Data promises huge benefits for medical research. Looking beyond superficial increases in the amount of data collected, we identify three key areas where Big Data differs from conventional analyses of data samples: (i) data are captured more comprehensivelyrelativeto the phenomenon under study; this reduces some bias but surfaces important trade‐offs, such as between data quantity and data quality; (ii) data are often analysed using machine learning tools, such as neural networks rather than conventional statistical methods resulting in systems that over time capture insights implicit in data, but remain black boxes, rarely revealing causal connections; and (iii) the purpose of the analyses of data is no longer simply answering existing questions, but hinting at novel ones and generating promising new hypotheses. As a consequence, when performed right, Big Data analyses can accelerate research. Because Big Data approaches differ so fundamentally from small data ones, research structures, processes and mindsets need to adjust. The latent value of data is being reaped through repeated reuse of data, which runs counter to existing practices not only regarding data privacy, but data management more generally. Consequently, we suggest a number of adjustments such as boards reviewing responsible data use, and incentives to facilitate comprehensive data sharing. As data's role changes to a resource of insight, we also need to acknowledge the importance of collecting and making data available as a crucial part of our research endeavours, and reassess our formal processes from career advancement to treatment approval.