Type I interferons are a widely expressed family of effector cytokines that promote innate antiviral and antibacterial immunity. Paradoxically, they can also suppress immune responses by driving production of anti‐inflammatory cytokines, and dysregulation of these cytokines can contribute to host‐mediated immunopathology and disease progression. Recent studies describe their anti‐inflammatory role in intestinal inflammation and the locus containing IFNAR, a heterodimeric receptor for the type I interferons has been identified as a susceptibility region for human inflammatory bowel disease. This review focuses on the role of type I IFNs in the intestine in health and disease and their emerging role as immune modulators. Clear understanding of type I IFN‐mediated immune responses may provide avenues for fine‐tuning existing IFN treatment for infection and intestinal inflammation.