The heterogeneity of sepsis poses an immense challenge to the long-term goal of personalising the treatment and management of sepsis patients. Novel techniques and platforms for multidimensional phenotyping of the sepsis patient’s host response have great potential as diagnostic and guiding tools for future sepsis management. In this recent review, EGIS members A. Cossarizza, M. Girardis and I. Rubio sift through the current state of the art on new tools and future concepts for the management of sepsis.