Antibiotics are the cornerstone of antibacterial therapy; however, the increasing development of resistant bacterial strains stresses the need for alternate approaches. Now, Puthia et al. target bacterial infection by boosting innate immunity. They found that a tight balance between the transcription factor interferon regulatory factor 7 (IRF-7) and its heterodimeric partner IRF-3 is critical for an efficient and self-limiting innate immune response to bacterial infection. Dysregulation of this balance contributed to kidney pathology in infected mice, and IRF7 attenuating polymorphisms associate with recurrent pyelonephritis in human children. Indeed, targeting IRF-7 protected mice against infection and renal tissue damage, suggesting that IRF7 could be a therapeutic target for protection against bacterial infection.