This chapter explores the twenty-first century transformation of R&D management, driven by disruptive technologies, economic instability, and global challenges like climate change. It examines the growing complexity of R&D, highlighting key challenges such as IP protection in the digital age, rapid technological obsolescence, interdisciplinary collaboration, and the intricacies of globalization, partnerships, and regulatory compliance. The chapter also emphasizes the importance of addressing skills gaps and fostering continuous learning to maintain competitiveness. Adapting to these challenges requires good organization and structure. To that end the chapter talks about how different agile methodologies, distributed or centralized teams, and cross-functional R&D structures can balance incremental and disruptive innovation. Strategies such as ambidextrous organizational designs, hybrid team models, and frameworks like the stage-gate process are presented to manage evolving demands. The chapter concludes by providing a practical framework for building adaptable R&D functions while setting the stage for a deeper exploration of leadership in innovation management.