Toll-like receptors (TLRs) are crucially important in the sensing of infectious agents. They serve to recognize pathogen-associated molecules and respond by triggering the induction of specific profiles of proteins that are tailored to the successful removal of the invading pathogens. The induction of TLR-responsive genes is mediated by the activation of transcription factors, and most interest has focussed on NF-κB, a transcription factor that is universally used by all TLRs. However, there has recently been a burgeoning effort to increase our appreciation of the importance of members of the interferon-regulatory factor (IRF) family in TLR signalling. This review will discuss the most recent findings relating to the regulation of IRF activity by TLRs and will highlight the rapidly increasing complexity of TLR signalling pathways.