All health systems and hospitals aim to provide high-quality, cost-effective healthcare for the communities they serve. Academic health systems take this mission one step further by providing a distinctive culture and environment where discoveries of all types may blossom: innovative therapeutics, novel processes, healthcare policies, and more. This chapter articulates the unique ways that academic health systems can leverage their patient-centered approach to innovation through their partnerships with universities and industries to test technologies and processes that improve healthcare delivery, quality, effectiveness, and efficiency. An academic health system can serve as a partnership facilitator, with interests and experiences that span the entire spectrum of university–industry (UI) partnership priorities. Such a facilitator can help stabilize a project when countercurrents unintentionally foil the altruistic endeavors organizations undertake. We identify and describe the unique benefits and challenges of working with academic health systems to innovate in the biomedical space. We examine a case study that illustrates the many facets of biomedical innovation and the strengths that academic health systems bring to UI partnerships. Finally, we contemplate a “values alignment model” wherein academic health systems can facilitate partnerships that meet industry, academic, hospital, and research goals by prioritizing patient care. Academic health systems augment UI partnerships by fostering a rich teaching environment, maintaining a robust patient population to validate new solutions, and nurturing a culture of innovation in the hearts and minds of physician-scientists and research teams.