The PERMIT project focuses on life-threatening infectious diseases, including the destructive necrotizing soft tissue infections (NSTI) and the large group of sepsis patients. The severity of these infections is dictated by the individual’s response to the pathogen and greatly depends on subject-specific host-pathogen interactions. For this reason, personalized therapeutic strategies targeting both the pathogen and host response are needed. To achieve this, PERMIT builds on the knowledge and resources created in the EU FP7-project INFECT including the world’s largest multicenter, prospectively enrolled patient cohort on NSTI, a biobank, multi-omics data, strategic data stewardship and pathophysiologic models. PERMIT will move towards preclinical validation of disease signatures, underlying mechanisms and biomarkers with the aim of translating these findings into improved or novel diagnostics, and to demonstrate the clinical feasibility and potential benefit of a personalized medicine approach to the treatment of sepsis and NSTI.