Rice is an important source of calories for more than one-third of the human population living on this planet. Several biotic, mesobiotic, and abiotic stresses limit the rice productivity. Among the biotic stresses, plant–parasitic nematodes are quite important. Root-knot disease of rice caused by Meloidogyne graminicola (Golden and Birchfield) is one of the most devastating and destructive disease of upland and rain-fed lowland rice (Oryza sativa L.) in Asia and Africa. In India, the disease is widespread in rice–wheat cropping system with significant yield losses. In deepwater rice, root-knot nematode infected seedlings remain stunted; unable to grow above flood water and perish due to continuous submergence the juveniles cause disruption, hypertrophy, and hyperplasia of cortical cells by intracellular migration and releasing esophageal gland secretions. This chapter reviews research on root-knot disease of rice and its pathogen M. graminicola during the past years in relation to etiology, host range, host–pathogen relationship and management through cultural and biological and biotechnological approaches.