Rhizobium-legume symbiosis represents a classical example of mutualism wherein, Rhizobium fixes inert nitrogen in the form of ammonia and equips it to plant; in return, plants provide shelter, mandatory source of carbon (dicarboxylic acids) and energy to the bacterium. Although nodulation is not a pre-requisite for leguminous plants but it has a selective advantage with respect to richness in protein (25%) enhancement as compared to wheat (10%). Perhaps, in symbiosis studies extra requirement for nitrogen is the key factor for selection of nitrogen fixation in legumes. Rhizobium infects leguminous host plants by way of growing root hairs to form nodules. Once specifically recognized, bacteria enter the cells of host plants through infection thread and infect its central tissue where they differentiate morphologically into nitrogen-fixing bacteroids. Important features of Rhizobium such as host-bacterium range, infection process, nodulation genes and its signaling have been elaborated. Studies on Rhizobium-legume symbiosis over the last 20 years, is gigantic, therefore, present chapter is restricted to plant-microbe interaction and its future prospects using biotechnological tools.