Septic shock remains a global health challenge with millions of cases every year, high rates of mortality and morbidity, impaired quality of life among survivors and relatives, and high resource use both in developed and developing nations. Care and outcomes are improving through organisational initiatives and updated clinical practice guidelines based on clinical research mainly carried out by large collaborative networks. This progress is likely to continue through the collaborative work of the established and merging trials groups in many parts of the world and through refined trial methodology and translational work. In this review, international experts summarize the current position of clinical research in septic shock and propose a research agenda to advance this field.