Effective program management is essential for successful elimination of malaria. In this perspective article, evidence surrounding malaria program management is reviewed by management science and malaria experts through a literature search of published and unpublished gray documents and key informant interviews. Program management in a malaria elimination setting differs from that in a malaria control setting in a number of ways, although knowledge and understanding of these distinctions are lacking. Several core features of successful health program management are critical to achieve elimination, including effective leadership and supervision at all levels, sustained political and financial commitment, reliable supply and control of physical resources, effective management of data and information, appropriate incentives, and consistent accountability. Adding to the complexity, the requirements of an elimination program may conflict with those of a control regimen. Thus, an additional challenge is successfully managing program transitions along the continuum from control to elimination to prevention of reintroduction. This article identifies potential solutions to these challenges by exploring managerial approaches that are flexible, relevant, and sustainable in various cultural and health system contexts.