Proponents of the learning region assert that investments should be made in the infrastructure that supports regionally-located innovative firms and that both institutional and governmental resources should be directed to drive the success of the regional innovation system. In this paper, we look at critical limitations to the realization of the learning region and at potential conflicts arising from the relative power of private and public interests in determining the learning region agenda. We draw on examples from Europe and the US, but pay special attention to the US case where the divide between regional economic development goals and the incentives driving the research university are particularly dramatic.