The first Government Chief Nursing Officer (CNO) position was created in New Zealand over a century ago. Over the ensuing decades, the roles of these national nurse leaders have evolved and become a focal point for global nursing and midwifery development. Despite the important actual and potential roles of CNOs, very little work has been done to systematically study the key issues that they face and the skill sets needed to address them. Now, in the face of global cost-driven health reform, the position of CNO is even more important than ever. This paper describes the only global systematic study of CNOs conducted since the beginning of health reform and lays a substantive foundation for the development of these key leaders and their positions. In addition, the research reported provides important groundwork for future studies and enhancement of the global literature relating to national nursing and midwifery leadership.