The future success of the translational research spectrum depends on the clinical research enterprise's ability to break through the barriers that constrain its productivity. As more basic science discoveries emerge, our ability to effectively translate this knowledge into improved patient care rests squarely on the manner in which we answer clinical questions. Informatics—the science of effective information use—is poised to help advance the conduct of science. However, incorporating informatics into the enterprise comes with its own set of challenges. To harness the benefits of improved information use, it is important to first establish how information flows within research. A thoughtful implementation of informatics—one that factors in social and organizational nuances—will undoubtedly lead to a more efficient and effective clinical research enterprise.