Oral mucositis (OM) is an important acute adverse effect of anticancer therapy. This condition presents high morbidity and may lead to the suspension of anticancer therapy. We reviewed the literature on the pathobiology of OM and the properties of erythromycin (EM), to consider the possibility of its use for the prevention and treatment of OM. We searched the PubMed, Scopus and Web of Science databases and selected complete articles published in English or Spanish that met the inclusion criteria. The search terms ?erythromycin?, ?inflammation?, ?immunomodulation? and ?oral mucositis? were used. The control of free radicals, transcription factors and pro-inflammatory cytokines has been considered as the key to the management of OM. EM has the ability to modulate oxidative stress, acts on the transcriptional system and inhibits the production of several cytokines that have been directly implicated in OM pathobiology. The present review suggests that EM could be effective in the treatment of OM. Experimental studies investigating the use of EM in OM should be encouraged.