Introduction The study of university spin-off activity has become a significant part of economic and management studies as the path from research to commercialization and is recognized as increasingly important to a country’s economic development. Entrepreneurial innovations in universities stimulate the economy through the development of new products, the creation of new industries and by contributing to employment and wealth creation (O’Shea et al. 2008). In areas like biotechnology, university research has led to the development of completely new industries that retain strong academic ties, highlighting how effective the relationship can be. In other areas, research and the transfer of technology within universities has been closely linked to the needs of local industry. Previous literature devoted to studying university spin-offs has covered a number of different perspectives. According to O’Shea et al. (2007), such perspectives include studies that explain spin-off creation in terms of the individuals who are involved in such activities; those that emphasize the organizational characteristics and resource endowments of universities; those that argue that social norms and institutional behaviour are determinants of spin-off activity; and those that argue that the wider social and economic context facilitates the creation of spin-off ventures. Although such work has undoubtedly provided universities with an improved understanding and awareness of spin-off behaviour, academic institutions are still faced with the challenge of identifying and replicating a process that facilitates successful entrepreneurial activities (O’Shea et al. 2008). The objective of this chapter is to assist in this challenge and explore the factors that contribute to the ability of academics to successfully commercialize opportunities for spin-off activity within universities. In doing this, we build on an existing conceptual framework outlined by O’Shea et al. (2008) and draw on additional existing literature to explore the factors in universities that can act as either a trigger for, or a barrier to, the successful implementation and commercialization of spin-off ventures. We then use these perspectives to inform a study of a single university, University College Dublin (UCD), which has been relatively successful at generating spin-off companies. Based on this study, we explore the factors that can either stimulate or inhibit an academic’s ability to commercialize a spin-off venture within a university environment.