Plants are under strong evolutionary pressure to maintain surveillance against pathogens. Resistance (R) gene-dependent recognition of pathogen avirulence (Avr) determinants plays a major role in plant defence. Here we highlight recent insights into the molecular mechanisms and selective forces that drive the evolution of NB-LRR (nucleotide binding-leucine-rich repeat) resistance genes. New implications for models of R gene evolution have been raised by demonstrations that R proteins can detect cognate Avr proteins indirectly by ‘guarding’ virulence targets, and by evidence that R protein signalling is regulated by intramolecular interactions between different R functional domains. Comparative genomic surveys of NB-LRR diversity in different species have revealed ancient NB-LRR lineages that are unequally represented among plant taxa, consistent with a Birth and Death Model of evolution. The physical distribution of NB-LRRs in plant genomes indicates that tandem and segmental duplication are important factors in R gene proliferation. The majority of R genes reside in clusters, and the frequency of recombination between clustered genes can vary strikingly, even within a single cluster. Biotic and abiotic factors have been shown to increase the frequency of recombination in reporter transgene-based assays, suggesting that external stressors can affect genome stability. Fitness penalties have been associated with some R genes, and population studies have provided evidence for maintenance of ancient R allelic diversity by balancing selection. The available data suggest that different R genes can follow strikingly distinct evolutionary trajectories, indicating that it will be difficult to formulate universally applicable models of R gene evolution.