Central to national economic competitiveness is the development of high growth Small and Medium sized Enterprises (SME’s). Besides their much reported role in job and wealth creation, SME’s worldwide have also shown remarkable flexibility to changing market conditions as well as a willingness to adopt new technologies and innovations. Against the background of the newly released South Africa’s national Department of Science and Technology’s 10 year Innovation Plan, the authors assert that one of the key parallel developments critical to ensure that the plan bears fruit is the growth and sustainability of innovative and technology driven SME’s and start-ups. This will require a comprehensive alignment of all government funded programmes and agencies to strengthen the congruency between enterprise development and national innovation and research commercialization drive. By citing recent developments in university-industry collaborations in South Africa, the authors argue that SME’s should be positioned to act as conduits for the exploitation of new technological innovations as well as commercialization of publicly funded research from South African Universities and other publicly funded Institutions.