In this mini review we discuss recent advances in the understanding of the N gene-mediated resistance to tobacco mosaic virus (TMV). The tobacco N gene belongs to toll-interleukin-1 receptor homology/nucleotide binding/leucine rich repeat (TIR-NB-LRR) class of resistance genes. It encodes two transcripts, NS and NL, by alternative splicing, both of which are required to confer resistance to TMV. The structure–function analysis of the N gene indicates that the TIR, NB and LRR domains are indispensable for its function. The N gene response is elicited by the C-terminal helicase domain of the 126 kDa TMV replicase protein. Tobacco N gene can also confer resistance to TMV in heterologous plants like tomato and Nicotiana benthamiana. Recent studies on N-mediated signalling suggest that EDS1, Rar1 and NPR1 genes play an important role in TMV resistance. Finally, we discuss current status of the N-mediated signal transduction and speculate directions for future work to understand N–TMV interaction.