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This article presents a discussion on the development of the activities of science, technology and innovation (S&T&I) in Cuba after 1959, the experiences gained and the challenges to face. The main topics to be discussed are: the different periods of this process and its main characteristics; the role of government and other innovation actors; the S&T&I planning and managerial model prevalent at different moments; the effects and outcomes of the fall of the European Socialist countries and the different measures taken to overcome the difficult situations encountered. Several case studies are presented: the development of biotechnology for medical purposes, and some results experienced in the basic industry sector. Some general conclusions are drawn, and some challenges and perspectives identified.