Medicago truncatula is able to perform a symbiotic association with Sinorhizobium spp. This interaction leads to the formation of a new root organ, the nodule, in which bacteria infect the host cells and fix atmospheric nitrogen for the plant benefit. Multiple and complex processes are essential for the success of this interaction from the recognition phase to nodule formation and functioning, and a wide range of plant host genes is required to orchestrate this phenomenon. Thanks to direct and reverse genetic as well as transcriptomic approaches, numerous genes involved in this symbiosis have been described and improve our understanding of this fantastic association. Herein we propose to update the recent molecular knowledge of how M. truncatula associates to its symbiotic partner Sinorhizobium spp.