After a period of proliferation of disease-specific initiatives, over the past decade and especially since 2005 many organizations involved in global health have come to direct attention and resources to the issue of health systems strengthening. We explore how and why such attention emerged. A qualitative methodology, process-tracing, was used to construct a case history and analyse the factors shaping and inhibiting global political attention for health systems strengthening. We find that the critical factors behind the recent burst of attention include fears among global health actors that health systems problems threaten the achievement of the health-related Millennium Development Goals, concern about the adverse effects of global health initiatives on national health systems, and the realization among global health initiatives that weak health systems present bottlenecks to the achievement of their organizational objectives. While a variety of actors now embrace health systems strengthening, they do not constitute a cohesive policy community. Moreover, the concept of health systems strengthening remains vague and there is a weak evidence base for informing policies and programmes for strengthening health systems. There are several reasons to question the sustainability of the agenda. Among these are the global financial crisis, the history of pendulum swings in global health and the instrumental embrace of the issue by some actors.