Abstract Proteins from the nucleotide-binding domain, LRR containing (NLR) family are involved in sensing bacterial invasion and danger signals in mammalian cells. Activation of these molecules leads to inflammatory responses which help clearance of invading pathogens. Recent data now shed light on the signal transduction pathways used by NLRproteins. This review summarizes advances in our understanding of signalling through NLRs with special emphasis on the Nod1 and Nod2 pathways.