Studies indicate that most European new, technology–based firms (NTBFs) have been founded by relatively senior, highly–educated personnel coming from existing companies. These founders already have strong, industry and market links. A relatively small proportion have spun out of university or other public research facilities. However, this latter group has attracted particular attention from several interested groups, including governments and the scientific establishment. For governments, this has appeared to offer a means whereby public policy could have a direct and significant impact on economic development. Hence substantial public resources are increasingly being committed to support these developments in most industrialised countries. The founders of HEI spinouts are often academics aiming to commercialise nascent technologies and they face challenges which are less likely to arise for the founder with an industry background. The emerging technologies often commercialised in academic spinouts may have many potential applications. At the outset founders must make critical strategic choices of applications to develop, if they are to attract the substantial resources often needed for the risky development process. Some of these choices need an understanding of changing fashions in business models and investors’ current preferences for particular industries. It is a difficult challenge for academic founders with little prior market knowledge and linkages, and no previous experience of professional investors and their requirements, to select the applications and business models which will support successful venture creation. This paper explores a number of key issues which surround these decisions and their relation to the changing business environment. It is concluded that the acceptability of novel technologies and products is mediated by systemic interactions which are ill–understood by industry and government.