Retention of faculty in academic medicine is a growing challenge. It has been suggested that inattention to the humanistic values of the faculty is contributing to this problem. Professional development should consider faculty members' search for meaning, purpose, and professional fulfillment and should support the development of an ability to reflect on these issues. Ensuring the alignment of academic physicians' inner direction with their outer context is critical to professional fulfillment and effectiveness. Personal reflection on the synergy of one's strengths, passions, and values can help faculty members define meaningful work so as to enable clearer career decision making. The premise of this article is that an awareness of and the pursuit of meaningful work and its alignment with the academic context are important considerations in the professional fulfillment and retention of academic faculty. A conceptual framework for understanding meaningful work and alignment and ways in which that framework can be applied and taught in development programs are presented and discussed.