Post-transcriptional RNA editing generates novel gene products by changing the coding sequence of the transcript from that in the genome. Two classes of RNA editing exist in mammals, each of which involves an enzymatic deamination. These reactions have stringent sequence and structural requirements for their target RNAs, and each requires distinctive enzymatic machinery. Alterations in the expression or abundance of RNA-editing factors produce unanticipated alterations in the processing or expression of RNAs, in some cases outside their physiological targets. Recent findings suggest that unregulated expression of the cytidine-deaminase gene family might lead to deamination of deoxycytidine nucleotides in DNA. Aberrant or dysregulated RNA editing, or altered expression of editing factors, might contribute to genomic instability in cancer.