The Triple Helix of university-industry-government interactions, highlighting the enhanced role of the university in the transition from industrial to knowledge-based society, has become widespread in innovation and entrepreneurship studies. We analyze classic literature and recent research, shedding light on the theoretical development of a model that has engendered controversy for being simultaneously analytical and normative, theoretical, practical and policy-relevant. We identify lacunae and suggest future analytical trajectories for theoretical development of the Triple Helix model. The explanatory power of Triple Helix has been strengthened by integrating various social science concepts, e.g. Simmel’s triad, Schumpeter’s organizational entrepreneur, institutional logics and social networks, into its framework. As scholars and practitioners from various disciplinary and inter-disciplinary research fields, e.g. artificial intelligence, political theory, sociology, professional ethics, higher education, regional geography and organizational behavior join Triple Helix studies or find their perspectives integrated, new directions appear for Triple Helix research.