Academic Health Centers are evolving to larger and more complex Academic Health Systems (AHS), reflecting financial stresses requiring them to become nimble, efficient, and patient (consumer) and faculty (employee) focused. The evolving AHS organization includes many positive attributes: unity of purpose, structural integration, collaboration and teamwork, alignment of goals with resource allocation, and increased financial success. The organization, leadership, and business acumen of the AHS influence directly opportunities for Departments of Medicine. Just as leadership capabilities of the AHS affect its future success, the same is true for departmental leadership. The Department of Medicine is no longer a quasi- autonomous entity, and the chairperson is no longer an independent decision-maker. Departments of Medicine will be most successful if they maintain internal unity and cohesion by not fragmenting along specialty lines. Departments with larger endowments or those with public financial support have more flexibility when investing in the academic missions. The chairpersons of the future should serve as change agents while simultaneously adopting a "servant leadership" model. Chairpersons with executive and team building skills, and business acumen and experience, are more likely to succeed in managing productive and lean departments. Quality of patient care and service delivery enhance the department's effectiveness and credibility and assure access to additional financial resources to subsidize the academic missions. Moreover, the drive for excellence, high performance and growth will fuel financial solvency.