This chapter aims at reflecting on some puzzling issues regarding the Global Health System that have been present throughout the collection of empirical evidence during the preparation of this book. From their specific angles, contributing authors in this volume have presented their point of view of the management of the Global Health System; they all point towards the complexity of managing such an open system. The first section of this chapter presents a characterization of the Global Health System and asks the question: under what conditions can the Global Health System actually be considered a system? Positioning the World Health Organization (WHO) within the Global Health System and analyzing its long-lasting quest for reforms will help raise issues related to governance. The second section of the chapter goes back to what appears to be one of the key features of the Global Health System, namely, the incomplete model for public health interventions during epidemics. This framework benefits from a general consensus among members of the Global Health System. However, this framework has been the subject of critique for quite some time, especially among social scientists, who have provided criticisms which seem to be regularly forgotten throughout the ranks of those responsible for global responses to epidemics. We therefore ask the question: what might be fueling this forgetfulness? However, somehow unsatisfied with this analysis, we sought out alternative frameworks. The third section of the chapter introduces what the literature on high reliability organizations (HRO) can bring to the table. Most notably, constant worries shared by the Global Health System and HRO revolve around striking a balance between prescription and autonomy, anticipation and adaptation, while retaining the necessity to cope with radical uncertainties, and the difficulties faced when organizing a highly diverse and fragmented workforce. It is hoped that the design principles of HRO might offer a fruitful path forward. Finally, the chapter concludes by arguing that, instead of continuing the calls for more structure, more control and more reforms, the Global Health System would benefit from decentralized emergency responses to health crises which rely on local expertise of all kinds, including the expertise of victims.