For a long time, the family of type I interferons (IFN-alpha/beta) has received little attention outside the fields of virology and tumor immunology. In recent years, IFN-alpha/beta regained the interest of immunologists, due to the phenotypic and functional characterization of IFN-alpha/beta-producing cells, the definition of novel immunomodulatory functions and signaling pathways of IFN-alpha/beta, and the observation that IFN-alpha/beta not only exerts antiviral effects but is also relevant for the pathogenesis or control of certain bacterial and protozoan infections. This review summarizes the current knowledge on the production and function of IFN-alpha/beta during non-viral infections in vitro and in vivo.