Technology has contributed to the advances on the genomic, transcriptomic, metabolomic and proteomic analyses of the plant-root-knot nematode (RKN) interaction. Holistic approaches to obtain expression profiles, such as cDNA libraries, differential display, q-PCR, microarray hybridization, massive sequencing, etc., have increased our knowledge on the molecular aspects of the interaction and have triggered the development of biotechnological tools to control this plague. An important limitation, however, has been the difficulty of cross-comparative analysis of these data. The construction of a database, NEMATIC, compiling microarray data available in Arabidopsis of the interaction with plant endoparasitic nematodes facilitated the in silico analysis, but is not sufficient for the handling of 'omic' information of different plant species. Omics combined with cell isolation techniques have shed some light on the heterogeneous expression signatures of nematode induced gall tissues, i.e., plant defences are specifically inhibited in giant cells within the gall aiding the nematode for a successful establishment. The natural resistance against RKNs varies from an early hypersensitive reaction before the establishment of the nematode, to the arrest of gall growth. The molecular bases of these mechanisms, not fully understood yet, could disclose powerful targets for the development of biotechnology based tools for nematode control.