The internationalization of Research and Development (R&D) has been extensively studied from an economical, industrial, and organizational perspective. However, at the R&D project level little has been reported in the literature. This paper presents the findings of a study of strategic issues and their influence on R&D project performance in transnational companies headquartered in Brazil or the US. The paper suggests that changes in our business environment have lead to more multinational R&D programs with implications for organizational process, leadership and business strategy. We identified five major shifts in R&D-based business environment that affect project planning and execution, and the way people work in teams. These paradigm shifts must be understood for managing and leading R&D organizations effectively, and for defining appropriate policy guidelines for aligning the R&D projects appropriately with the overall enterprise strategy. Further, the results suggest a need for structuring management processes that deal with these changes and strategic issues. A better understanding of the dynamics and degree to which these issues impact project performance should help managers in fine-tuning their business processes, support systems and management styles to achieve increased resource effectiveness and competitiveness.