Making progress on the 'grand challenge' issues facing society demands productive collaboration among academics and stakeholders both within and across disciplines and sectors. To facilitate such collaborations, higher education institutions convene a range of organizational structures intended to promote productive interactions. These structures carry a variety of names: centers, institutes, collaboratives, and laboratories, among others. Based on observation of the academic landscape for several decades, few of these entities realize their potential to make a substantive difference on the issue(s) they were created to address. In this paper we review the experiences of two University-based Centers that have had sustained impact over more than three decades. We offer thoughts on key success factors for cross-mission, cross-disciplinary and disciplinary convening structures that may be useful for those looking to establish such entities and/or re-boot existing Centers. Key elements discussed include a clear need for the Center; institutional support; incentives for faculty to engage; access to essential resources; a viable revenue model; flexibility and adaptability; and effective leadership and governance. Specific examples for how each of these elements have been operationalized in the Global Trade Analysis Project and the Center for Food and Agricultural Business, both at Purdue University, are provided.