A redefinition of leadership roles was necessitated by the adoption of program management, which accompanied the merger of two large academic hospitals, each of which consisted of two sites. Directors of professional departments were removed when staff were deployed to programs. Program directors were selected to manage the new programs, and profession leaders were identified to monitor standards of practice. The roles and accountabilities of the new program and profession leaders needed to be clarified for incumbents and other hospital staff. This article describes the process undertaken to clarify those responsibilities. The resulting Guide outlines 14 specific and collaborative responsibilities of program and profession leaders. Plans for review and future development of the Guide are discussed.