This paper discusses the significance, trends and achievements of the entrepreneurship and small and medium-sized enterprise policy in Andalusia developed with the support of the European Regional Development Fund (ERDF). The lack of entrepreneurial culture and business environment conditions unfavourable to entrepreneurship have traditionally acted as structural obstacles to regional development in Andalusia. In order to face this problem, the role of the entrepreneurship policy within the strategy for regional development has increased over the programming periods of the European Cohesion policy. This article proposes some recommendations for a more effective and efficient design of the Cohesion policy in this field drawing on the analysis of the experience of Andalusia.