In recent years, grand challenge initiatives have emerged nationally with the goal of addressing large, multidisciplinary public problems. The advent of university-led grand challenge initiatives offers an important opportunity to reflect on how institutions of higher education design, implement, and orient externally relevant activities at a time of public skepticism. With a focus on public problem solving, grand challenge initiatives offer a way to re-engage the public's imagination and faith in higher education, depending on what these initiatives reflect about institutional values, practices, and work. We use this reflection opportunity to review early approaches to university-led grand challenge initiatives. We then propose that two frameworks should merge explicitly into grand challenge initiatives to guide public problem solving: community engagement and collective impact. Finally, we offer the establishment of a grand challenge initiative at the University of Denver (DU) as an example of the integration of community engagement and collective impact frameworks into the organization and implementation of institution-wide, publicly-engaged work.