Why do some global health initiatives receive priority from international and national political leaders whereas others receive little attention? To analyse this question we propose a framework consisting of four categories: the strength of the actors involved in the initiative, the power of the ideas they use to portray the issue, the nature of the political contexts in which they operate, and characteristics of the issue itself. We apply this framework to the case of a global initiative to reduce maternal mortality, which was launched in 1987. We undertook archival research and interviewed people connected with the initiative, using a process-tracing method that is commonly employed in qualitative research. We report that despite two decades of effort the initiative remains in an early phase of development, hampered by difficulties in all these categories. However, the initiative's 20th year, 2007, presents opportunities to build political momentum. To generate political priority, advocates will need to address several challenges, including the creation of effective institutions to guide the initiative and the development of a public positioning of the issue to convince political leaders to act. We use the framework and case study to suggest areas for future research on the determinants of political priority for global health initiatives, which is a subject that has attracted much speculation but little scholarship.