The science of team science encompasses an amalgam of conceptual and methodologic strategies aimed at understanding and enhancing the outcomes of large-scale collaborative research and training programs. This field has emerged rapidly in recent years, largely in response to growing concerns about the cost effectiveness of public- and private-sector investments in team-based science and training initiatives. The distinctive boundaries and substantive concerns of this field, however, have remained difficult to discern. An important challenge for the field is to characterize the science of team science more clearly in terms of its major theoretical, methodologic, and translational concerns. The articles in this supplement address this challenge, especially in the context of designing, implementing, and evaluating cross-disciplinary research initiatives. This introductory article summarizes the major goals and organizing themes of the supplement, draws links between the constituent articles, and identifies new areas of study within the science of team science.