Type I interferon-alpha/beta play an essential role in immunity to viruses. While interferon-beta has been used as a model of a complex promoter, many of the signalling pathways leading to interferon-beta gene expression remain controversial. Recent milestones include the discovery of Toll-like receptors and RNA helicases that signal via a novel kinase complex composed of I kappa B kinase-iota/epsilon or TANK binding kinase-1. This review provides a timely summary of this rapidly expanding field, focusing specifically on the various viral RNA binding molecules and their associated signalling pathways.