Root-knot nematodes (RKNs), genus Meloidogyne, are widespread, polyphagous endo-parasites which present a serious and growing threat to agriculture. They have evolved sophisticated strategies for exploiting plants, and research on nematode parasitism therefore tackles fundamental questions in plant development and host defence. These obligate biotrophic pathogens establish and maintain an intimate relationship with their host plants. They induce major changes in plant cells, leading to the development of the specialized hypertrophied and multinucleate feeding cells essential for nematode growth and development. RKNs have a wide host range, suggesting that they can probably hijack fundamental host functions. Nematode-secreted proteins (effectors) are thought to be instrumental in the manipulation of developmental and defence signalling pathways in host cells, particularly during the initiation and maintenance of nematode feeding cells. Three oesophageal secretory gland cells that undergone considerable adaptation to increase their secretory activity are the main source of these effector proteins. Several molecular approaches have been used to identify and functionally characterize the effectors produced by nematode secretory organs. About 100 RKN parasitism genes have been cloned and effectors have been shown to be delivered to the apoplasm, cytoplasm and nucleus of host cells. The first host targets and functions of secreted effector proteins have recently been elucidated. In this chapter, we describe the complex interactions between RKNs and their infected hosts and highlight the progress made in the molecular and functional characterization of RKN effector proteins and our understanding of host plant cell manipulation by these parasites.