Root-knot nematodes (RKNs) are ubiquitous parasites with an amazing capacity to interact with a very large variety of plant species. They are sedentary endoparasitic nematodes that depend on the induction of a permanent feeding site in living roots to complete their life cycle. RKNs interfere with the genetic programmes of their hosts to transform root vascular cells into giant cells (GCs) through the injection of nematode effectors from their oesophageal glands. Dramatic rearrangements in GCs cytoskeleton, alteration of cell cycle mechanisms, such as mitosis and endoreduplication, readjustment of enzymes involved in carbohydrate synthesis and degradation are among those processes modified in GCs. GCs act as sinks to provide nutrients for life cycle completion from J2 larvae to adult females. The female produces an egg offspring protected by a gelatinous matrix and the free-living stage, J2, hatch from these eggs, completing the nematode life cycle. The model species Arabidopsis thaliana allowed easy in vivo observations of the interaction by video-enhanced contrast light microscopy on infected roots, and the wide range of existing genetic and molecular tools of this plant model has extended its use. Holistic approaches to tackle gene expression combined with cell biology techniques, as isolation of GCs by laser capture microdissection, allowed GC-specific transcriptomic analysis, generating vast lists of differentially expressed genes. However, the design of consistent functional hypothesis about these genes and their products will require the development of in silico analysis tools for comparisons among the transcriptomes of plantenematode compatible interactions. The understanding of the processes subjacent to GC differentiation and maintenance, as well as a deeper knowledge of RKN mode of parasitism, will provide tools for new control methods of these devastating agricultural pests.