Symbiosis is a close and often long-term interaction between two different biological organisms, i.e. plants or fungi and microorganisms. Two main types of plant–microorganism interactions, mutualistic and cooperative, have been categorized. Mutualistic interactions, including nitrogen-fixing and mycorrhizal symbioses, refer to mostly obligate relationships between a host plant and a symbiont microorganism. Cooperative interactions correspond to less obligate and specific relationships. They involve microorganisms, referred to as plant growth-promoting rhizobia (PGPR), able to colonize root surface or inner tissues. Lichens are symbiotic associations of host fungi and photosynthetic partners that may be Cyanobacteria or green algae. Increasing evidence has been reporting the presence of nitric oxide (NO) during symbiotic interactions. Most of the time, both the plant and the microorganism partners participate in NO production and catabolism. At early stage of the symbiosis, NO was shown to be potentially involved in the repression of plant defence reactions, favouring the establishment of the plant–microbe interaction. At later stages of the interactions, NO was shown to inhibit nitrogen fixation, but it was also demonstrated to have regulatory roles in nitrogen and carbon metabolisms, to play a beneficial metabolic function for the maintenance of the energy status under hypoxic conditions, to cross-react with hormone and reactive oxygen species pathways and to be potentially involved in the set-up of senescence processes. The present review provides an overview of NO production and many-faceted effects in symbiotic interactions and presents several tracks which appear to be particularly promising to decipher the roles of NO in plant–microbe symbioses.