The pathogenesis of inflammatory bowel disease (IBD) is still unclear, but includes both inflammatory and autoimmune reactions. Current methodological approaches could better elucidate the cytokine pathways and the genetics involved in the etiopathogenesis of this disease. Interferons (IFNs) are cytokines that play a key role in autoimmune/inflammatory disorders because of their pro-and anti-inflammatory properties as well as their immunoregulatory functions. An increased expression of IFN-regulated genes, widely known as an IFN signature, has been reported in blood and tissue from patients with autoimmune disorders. In this review, we present the function as well as the clinical and therapeutic potential of the IFN signature. Current data demonstrate that the IFN signature can be used as a biomarker that defines disease activity in autoimmune diseases, although this has not been thoroughly studied in IBD. Consequently, further investigation of the IFN signature in IBD would be essential for a better understanding of its actions.