NBS-LRR genes are the major class of disease resistance genes in flowering plants, and are arranged as single genes and as clustered loci. The evolution of these genes has been investigated in Arabidopsis thaliana by combining data on their genomic organisation and position in phylogenetic trees. Tandem and segmental duplications distribute and separate NBS-LRR genes in the genome. It is, however, unclear by which mechanism(s) NBS-LRR genes from different clades are sampled into heterogeneous clusters. Once physically removed from their closest relatives, the NBS-LRR genes might adopt and preserve new specificities because they are less prone to sequence homogenization.