The concept of “big data” is nothing new to physicians. Every day, physicians make clinical decisions based on years of didactic and inductive lessons from patients gone by. By contrast, academic researchers have only recently been armed with easy access to new computational resources and statistical tools—in other words, big data. Unfortunately, while researchers are rewarded for theory and mechanism, practitioners call for solutions and pragmatism. The real promise for big data is fulfilled through researchers asking harder, more powerful questions that matter to clinicians and patients right now.