There has long been a tension between the roles of the university in servicing the needs of sub‐national economies and civil societies, those of the national state and those of learning and the pursuit of knowledge in an abstract sense. The position in liberal democracies through much of the twentieth century can be accurately characterized by a significant degree of separation and segregation between the university, the state and the market. Recently, however, it has been posited that the balance is shifting away from relative autonomy towards a new ‘mode of knowledge production’ in which the growing engagement of universities with their regions and localities is an important aspect. The first part of this article explores the knowledge economy rhetorics which have come to dominate public policy rationales in many liberal democracies and interrelationships with questions of territory and scale. Second, the implications for universities are considered as they are confronted by a number of challenges and choices in navigating the waters of increasing societal expectations. Finally, the article highlights key questions that emerge from our preliminary overview of these issues within a wider research agenda around universities, the knowledge economy and regional development.