Plant health is strongly influenced by the interactions between parasites/pathogens and beneficial microorganisms. In this chapter we will summarize the up-to date knowledge on soil suppressiveness as a biological tool against phytonematodes and explore the nature of monoculture versus crop rotation in this regard. Since nematodes are successfully antagonized by different microbiological agents, we highlighted this phenomenon with respect to the most important antagonists, and a nature of these interactions. The focus is on the hyperparasitic microbes of phytonematodes such as Pasteuria sp. and egg parasites. Furthermore, we comprised the studies on the defence system expressions in plants triggered by nematode-associated microbes. The attachment of bacteria and fungi to phytonematodes and putative effects of the attachment on the induced systemic resistance in plants are discussed. Finally, our chapter is rounded up with the importance of incorporating the knowledge on plant-nematode-microbe interactions in the integrated pest management.