The symbiotic interaction between legumes and bacteria of Rhizobium type leads to the formation of new organs, called nodules, which provides a niche for bacterial nitrogen (N-2) fixation. In the nodules, bacteria differentiate into bacteroids able to fix atmospheric N-2 through nitrogenase activity. As nitrogenase is strongly inhibited by oxygen, N-2-fixation is made possible thanks to microaerophilic conditions prevailing in the nodules, characterized by a balance between low oxygen contents and adjusted nitric oxide (NO) contents. NO was shown to be produced by both the plant and bacterial partners during symbiosis, from early interaction steps between the plant and the bacteria to N-2-fixing and senescence steps in mature nodules. NO is required for an optimal establishment of the symbiotic interaction. Transcriptomic analysis at early stage of the symbiosis showed that NO regulates about 2030 genes including genes involved in the induction of cell dedifferentiation and organogenesis, and in the repression of plant defense reactions, favouring the establishment of the plantemicrobe interaction. In mature nodules, NO was found to act as both an inhibitor of N-2-fixation, a regulator of nitrogen metabolism, a beneficial metabolic intermediate for the maintenance of the energy metabolism under hypoxic conditions and a signal triggering nodule senescence. The present review provides an overview of NO sources and degradation pathways and of its multifaceted functions throughout the whole symbiotic process. It additionally analyses NO crosstalks with reactive oxygen species and hormones and presents particularly promising issues to decipher the roles of NO in N-2-fixing symbioses.