Academic medicine is in an era of unprecedented and constant change due to fluctuating economies, globalization, emerging technologies, research, and professional and educational mandates. Consequently, academic health science centers (AHSCs) are facing new levels of complexity, constraint, and uncertainty. Currently, AHSC leaders work with competing academic and health service demands and are required to work with and are accountable to a diversity of stakeholders. Given the new challenges and emerging needs, the authors believe the leadership methods and approaches AHSCs have used in the past that led to successes will be insufficient. In this Article, the authors propose that AHSCs will require a unique combination of old and new leadership approaches specifically oriented to the unique complexity of the AHSC context. They initially describe the designer (or hierarchical) and heroic (military and transformational) approaches to leadership and how they have been applied in AHSCs. While these well-researched and traditional approaches have their strengths in certain contexts, the leadership field has recognized that they can also limit leaders’ abilities to enable their organizations to be engaged, adaptable, and responsive. Consequently, some new approaches have emerged that are taking hold in academic work and professional practice. The authors highlight and explore some of these new approaches—the authentic, self, shared, and network approaches to leadership—with attention to their application in and utility for the AHSC context.