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The genus Azospirillum comprises plant-growth-promoting bacteria (PGPB), which have been broadly studied. The benefits to plants by inoculation with Azospirillum have been primarily attributed to its capacity to fix atmospheric nitrogen, but also to its capacity to synthesize phytohormones, in particular indole-3-acetic acid. Recently, an increasing number of studies has attributed an important role of Azospirillum in conferring to plants tolerance of abiotic and biotic stresses, which may be mediated by phytohormones acting as signaling molecules. Tolerance of biotic stresses is controlled by mechanisms of induced systemic resistance, mediated by increased levels of phytohormones in the jasmonic acid/ethylene pathway, independent of salicylic acid (SA), whereas in the systemic acquired resistance-a mechanism previously studied with phytopathogens-it is controlled by intermediate levels of SA. Both mechanisms are related to the NPR1 protein, acting as a co-activator in the induction of defense genes. Azospirillum can also promote plant growth by mechanisms of tolerance of abiotic stresses, named as induced systemic tolerance, mediated by antioxidants, osmotic adjustment, production of phytohormones, and defense strategies such as the expression of pathogenesis-related genes. The study of the mechanisms triggered by Azospirillum in plants can help in the search for more-sustainable agricultural practices and possibly reveal the use of PGPB as a major strategy to mitigate the effects of biotic and abiotic stresses on agricultural productivity.