The purpose of this paper is to examine the evolution of regional enterprise policies and associated governance mechanisms in the UK to address the following questions: how are evolving systems of regional governance in the UK impacting on the capability of regional policy to foster entrepreneurship? To what extent does enterprise policy form a key part of the overall economic development strategy of regions? And are different forms of regional enterprise policy and priorities emerging? The study draws on a series of key interviews with policy makers across the regions of Wales, Scotland and England (using the case study of the Yorkshire and the Humber region). The approach adopted in this study facilitates an exploration of the perspectives of those responsible for the formulation and delivery of such support. The paper seeks to ascertain and analyse policy maker opinion on the nature of previous policy, as well as future requirements if policies are to become more effective. It focuses on the period from 1997, with the election of the Labour Government, and the period from 2010 to 2015 represented by the Conservative-Liberal Democratic Coalition Government. The author concludes that regional entrepreneurship differentials emerge due to the spatial and place-based nature of three underlying factors: first, the nature of markets; second, the nature of innovation systems; and third, the nature of place-based cultures, communities and the institutions they establish. In the regions studied, failings and limitations in these factors suggest two potential requirements: first, the introduction of public policy in the form of a range of interventions and support mechanisms, second, the introduction of a system of policy governance to establish appropriate interventions and support mechanisms. In the case study regions, clear attempts have been made to address each of the three limiting factors through a range of policy and governance systems, but due to a complex range of issues these have often achieved limited success.