Companies and universities are critical sources of research and innovation. Whereas each sector has achieved success on its own, purposeful engagement presents opportunities to accelerate success for mutual and public benefit. In this chapter, we explain the key concepts of our book within a theme of alignment of goals between university and industry, achieving “innovation at the interface.” We draw from the experiences of skilled practitioners who have contributed to the University Industry Demonstration Partnership (UIDP), and introduce examples of successful University-Industry (UI) engagement. We also draw from the insights of academicians who have studied innovation processes and provide a comprehensive view of how UI engagement has evolved over time. Though the challenges of UI engagement are many—as we describe—they can be overcome. We offer a guide to successful UI engagement.