In 2003, the European Commission established the principle of coexistence which refers to 'the ability of farmers to make a practical choice between conventional, organic and GM-crop production, in compliance with the legal obligations for labelling and/or purity standards' and laid down guidelines defining the context of this coexistence. In order to determine what is needed for the sustainable introduction of GM crops in Europe, the cross-disciplinary SIGMEA Research Project was set up to create a science-based framework to inform decision-makers. SIGMEA has (i) collated and analysed European data on gene flow and the environmental impacts of the major crop species which are likely to be transgenic in the future (maize, rapeseed, sugar beet, rice, and wheat), (ii) designed predictive models of gene flow at the landscape level, (iii) analysed the technical feasibility and economic impacts of coexistence in the principal farming regions of Europe, (iv) developed novel GMO detection methods, (v) addressed legal issues related to coexistence, and (vi) proposed public and farm scale decision-making tools, as well as guidelines regarding management and governance. This publishable version of the final activity report of the FP6 SIGMEA research project, covers the fourteen major issues under investigation.