This article explores the way in which Smart Specialisation has been integrated in the programming and implementation of the ESIF Operational Programmes of countries and regions which are partners in the IQ-Net Network – a network for improving the quality of Structural Funds programme management through exchange of experience. It discusses the design of Smart Specialisation Strategies through entrepreneurial discovery, the implementation of the strategies as part of the ESIF programmes, and the lessons learnt so far. It shows that the Smart Specialisation approach, albeit not novel in all cases, is considered on the whole as useful and to have contributed to better prioritisation and more joined-up policy-making. However, these are still early days and success will rest on effective implementation. This will require on-going engagement with stakeholders, to test and refine the validity of assumptions and choices made, and above all continued political endorsement to support cross-sectoral working and hold the private sector to account on their commitments to the strategy. The focus should now be placed on ensuring that implementation rises to the challenge and that adequate support is provided to regional and national authorities and to all types of stakeholders, throughout the life of the ESIF programmes, to allow them to continue to drive the Smart Specialisation approach through.