University-industry-government interaction is the key to improving conditions for innovation in a knowledge-based society. A second academic revolution aimed at integrating economic and social development (third mission) is transforming traditional university teaching and research into a university education intended for entrepreneurs. This paper thus analyses the evolution of the university/socio-economic environment relationship, the models used for explaining innovation and those encouraging innovation. Debate concerning new missions, research and a third mission are then presented. The previous elements may help determine new challenges facing Latin-American universities.