People who administer organizations of various types, including medical practices, are finding it increasingly necessary to demonstrate leadership. The challenge is to understand the meaning of effective leadership and to have guiding principles with regard to its implementation. It is argued here that responsibility represents a key guiding theme that doctors and practice managers can use to chart their day-to-day actions as leaders. Responsibility implies accountability to a broad array of groups and individuals who increasingly expect that leaders act in a manner that is aligned with their interests. This new era of leader accountability raises the question, to whom and what are organizational leaders responsible? In an attempt to answer this question, The author elaborates a broad perspective of responsible leadership and address both internal and external stakeholders to which a leader is responsible. Recommendations and principles are provided for how to balance the needs and interests of various stakeholders when leading one’s practice. The article ends with a consideration of important caveats with regard to responsible leadership.