RNA damage has been recently reported to increase under oxidative stress and in patients with many degenerative diseases, which has drawn attention to the consequences of RNA oxidation at the molecular and cellular levels. Under similar conditions the levels of oxidative damage in RNA are usually higher than those in DNA, which may impair protein synthesis or other RNA function. Therefore, accumulation of RNA damage must be prevented and cells have developed specific mechanisms to remove oxidatively-damaged RNA and to block incorporation of oxidized nucleotides during RNA synthesis. Removal of oxidized RNA may be mediated by specific proteins that recognize oxidative lesions and direct the RNA degradation machinery to eliminate the damaged RNAs. During RNA synthesis, oxidized ribonucleotides are hydrolyzed or discriminated from normal ribonucleotides during transcription, preventing their incorporation into RNA. Collective evidence suggests that RNA oxidative damage is a challenging and persistent problem normally controlled through RNA surveillance mechanisms, making them critical to maintaining cellular health and preventing disease.