Viral infection is detected by the innate immune system which mounts a rapid semi-selective defence involving inflammation and production of type 1 interferons. Several sensors, both cell surface and intracellular, exist to detect different types of viral motifs. Double-stranded RNA viruses and dsRNA replication intermediates are detected by tolllike receptor 3 (TLR3) as well as by retinoid-inducible gene 1 (RIG-I) like receptors. Binding of dsRNA or its synthetic analogue poly I:C to TLR3 recruits the adaptor protein TRIF and stimulates distinct pathways leading to activation of interferon regulatory factor (IRF) and NF-B. Here, we review the signalling cascades initiated by TLR3 and the modulation of these pathways.