Toll-like receptors (TLRs) are crucially important in the sensing of viral infections and viral nucleic acids. TLR triggering leads to the induction of specific intracellular signaling cascades that result in the activation of two major families of transcription factors; the IFN-regulatory factors (IRFs) and nuclear factor-kappa B (NF-kappaB). IRFs and NF-kappaB work together to trigger the production of type I interferons (IFNalpha/beta) or inflammatory cytokines leading to the maturation of dendritic cells and the establishment of antiviral immunity. This review will focus on the most recent findings relating to the regulation of IRF activity by TLRs, highlighting the increasing complexity of TLR-mediated signaling pathways.