This article highlights the various ways in which the relationship between universities and cities has been understood in different contexts and the tensions which emerge. A framework for understanding is then presented via a broader discussion of governance, institutions and mediation. Mediation is particularly important as a unifying principle. Global or convergent pressures are translated, reflected, refracted, absorbed and magnified by governance systems, formal policies and local contexts. The interests, values and assumptions and pre-reflexive and reflexive understandings of urban institutions and actors are often overlooked in analyzing university-city interactions. This framework serves not only to structure this issue, but to offer suggestions for further work in this field of research, policy and practice.