The immune system protects us from infections by detecting and eliminating invading pathogens. These two strategies form the basis of conventional clinical approaches in the fight against infectious diseases. In the latest issue of the journal Science, Miguel Soares from the Instituto Gulbenkian de Ciência (Portugal) along with Ruslan Medzhitov from Yale University School of Medicine and David Schneider from Stanford University propose that a third strategy needs to be considered: tolerance to infection, when the infected host protects itself from infection by reducing tissue damage and other negative effects caused by the pathogen or the immune response against the invader. The authors argue that identifying the mechanisms underlying this largely overlooked phenomenon may pave the way to new strategies to treat many human infectious diseases.