Plant resistance is currently the most effective and environmentally safe method to control plant parasitic nematodes (PPNs). Resistance genes generally act against sedentary PPNs by inducing a hypersensitive reaction that prevents the parasite installation and/or reproduction. However, the recent emergence of virulent biotypes able to overcome the plant resistance genes may constitute a severe limitation to this control strategy. In selection experiments conducted under controled environment, the genetic variation, specificity and inheritance of nematode virulence have been demonstrated. Moreover, the occurrence of gene-for-gene interactions has been shown in a few cases. Moleculars markers have been extensively used to investigate the genetic variability of PPNs, but so far, the genomic polymorphisms observed are largely independent of virulence. Such data suggest that, within a species, virulent isolates do not share a common origin, but are probably the result of independent mutational events. To understand the molecular mechanisms responsible for virulence in PPNs, several strategies have been developed, in relation with their mode of reproduction (parthenogenesis versus amphimixis). As an example, recent results obtained in our laboratory on the root-knot nematodes Meloidogyne spp. are presented. On a more general point of view, factors that may induce stable genome variability in PPNs, e.g. transposition of mobile elements and chromosomal rearrangements (leading to polyploidy, aneuploidy, etc) will also be considered. Advances in knowledge in these areas should have important consequences for the management and durability of natural resistance genes, and for the engineering of new forms of resistance.