Physician leaders with established clinical reputations are an asset to health systems in a changing healthcare environment. Surgeons in particular are uniquely qualified to lead at the health system level and impact hospital operations and care delivery. The purpose of this chapter is to highlight the strengths that serve surgeon leaders well and discuss the specific challenges and opportunities that exist as they assume broader leadership roles. Some common system-level roles are defined here, and options for acquiring additional needed skills are outlined. There is a significant opportunity for strong clinical leaders to expand their influence outside of the clinical domain and pursue non-conventional leadership paths in health care.