Universities have become fundamental actors in the emergence and strengthening of Regional Innovation Systems (RIS), which promote the development in the countries that comprise them. SRI, the leading role of universities in their management and the role of governments in their development will be addressed from 3 main elements. The first involves the generality of the SRI and the context of their evolution. The second corresponds to the fundamental role of universities in the development of these systems and how they can influence in their successful implementation. Finally, it refers the university-state-enterprise relationship as synergies generator in the configuration of an SRI. It is concluded that the consolidation of a SRI allows the social, economic, industrial and technological development of the geographic area in which it is configured through mechanisms of knowledge capitalization with strategies such as Spin Off that are generated in universities.