Firms use R&D partnerships to access knowledge and build global R&D networks. This article develops an integrated framework to examine the determinants of the choice of partners with which firms co-operate on R&D. This resource-based perspective underscores the interactions between three major questions: why co-operate, who does and with whom? It argues in particular that the choice of partners is dictated by the complementary resources which the latter command. The framework is then expanded to predict the relative efficiency of R&D co-operation with different partners, including suppliers, clients, rivals, academic institutions and foreign firms. The empirical analysis, which is based on responses to France’s version of the second European community innovation survey (CIS-2), strongly supports the overall framework of analysis.