In a healthcare context in which research evidence is not used routinely in practice, there have been increasingly loud calls for the use of theory from investigators working in the field of knowledge translation. Implementation researchers argue that theory should be used to guide the design of testable and practical intervention strategies, and thus, contribute to generalizable knowledge about implementation interventions. The purpose of this commentary is to critique model papers writing by a team of scholars who aimed to disentangle some of the relationships determining research utilization, by scrutinizing an existing conceptual framework that acknowledges, along with other factors, the importance of contextual factors in knowledge translation. These papers are used as a vehicle to explore theory application in knowledge translation research. As theory use and development is in its infancy, some key issues, including different ideological perspectives, factors for and against theory use, ensuring conceptual clarity, selecting coherent overarching frameworks, and choosing appropriately among theories, are considered. Finally, an agenda for theory-informed research is outlined, which highlights the need for scholarly, pluralistic, and collaborative activity if the state of knowledge translation science is to advance.