[u]Significance[/u]: During the Legume–Rhizobium symbiosis, hydrogen peroxide (H2O2) and nitric oxide (NO) appear to play an important signaling role in the establishment and the functioning of this interaction. Modifications of the levels of these reactive species in both partners impair either the development of the nodules (new root organs formed on the interaction) or their N2-fixing activity. [u]Recent Advances[/u]: NADPH oxidases (Noxs) have been recently described as major sources of H2O2 production, via superoxide anion dismutation, during symbiosis. Nitrate reductases (NR) and electron transfer chains from both partners were found to significantly contribute to NO production in N2-fixing nodules. Both S-sulfenylated and S-nitrosylated proteins have been detected during early interaction and in functioning nodules, linking reactive oxygen species (ROS)/NO production to redox-based protein regulation. NO was also found to play a metabolic role in nodule energy metabolism. [u]Critical Issues[/u]: H2O2 may control the infection process and the subsequent bacterial differentiation into the symbiotic form. NO is required for an optimal establishment of symbiosis and appears to be a key player in nodule senescence. [u]Future Directions[/u]: A challenging question is to define more precisely when and where reactive species are generated and to develop adapted tools to detect their production in vivo. To investigate the role of Noxs and NRs in the production of H2O2 and NO, respectively, the use of mutants under the control of organ-specific promoters will be of crucial interest. The balance between ROS and NO production appears to be a key point to understand the redox regulation of symbiosis.