The management of febrile patients is one of the most common and important problems facing healthcare providers. Distinction between bacterial infections and trivial viral infection on clinical grounds is unreliable, and as a result innumerable patients worldwide undergo hospitalization, invasive investigation and are treated with antibiotics for presumed bacterial infection when, in fact, they are suffering from self-resolving viral infection. We aim to improve diagnosis and management of febrile patients, by application of sophisticated phenotypic, transcriptomic (genomic, proteomic) and bioinformatic approaches to well characterised large-scale, multi-national patient cohorts already recruited with EU funding. We will identify, and validate promising new discriminators of bacterial and viral infection including transcriptomic and clinical phenotypic markers. The most accurate markers distinguishing bacterial and viral infection will be evaluated in prospective cohorts of patients reflecting the different health care settings across European countries. By linking sophisticated new genomic and proteomic approaches to careful clinical phenotyping, and building on pilot data from our previous studies we will develop a comprehensive management plan for febrile patients which can be rolled out in healthcare systems across Europe.