Molecular data regarding the diversity of plant loci involved in resistance to herbivores or pathogens are becoming increasingly available. These genes demonstrate variable patterns of diversity, suggesting that they differ in their evolutionary history. In parallel, the study of natural variation for resistance, generally conducted at the phenotypic level, has shown that resistance does not evolve solely under selection pressures exerted by enemies. Metapopulation dynamics and other ecological characteristics of interacting species also appear to have a large impact on resistance evolution. Until now, studies of resistance at the molecular level have been conducted separately from ecological studies in extant populations. Future progress requires an evolutionary approach integrating both molecular and ecological aspects of resistance evolution. Such an approach will contribute greatly to our understanding of the evolution of molecular diversity at loci involved in biotic stress.