The sequencing of genomes from higher organisms demonstrated that the number and complexity of expressed mRNA sequences and proteins exceeds the quantity of predicted genes. This disparity has been attributed to a variety of cellular mechanisms including the use of alternative promoters, mRNA splice sites and/or polyadenylation sites. Additionally, single nucleotide modifications within RNA, and more recently DNA, can generate diversity in protein expression. C to U or dC to dU modification at specific sites within RNA or DNA can arise from targeted editing activities rather than spontaneous mutation and is catalyzed by APOBEC-1 or related zinc-dependent, cytidine deaminases. The function and substrate specificity are known for only five of the ten deaminases in the APOBEC-1 Related Protein family. Hence, exciting discoveries are predicted regarding the role of editing enzymes as modifiers of protein expression in normal physiology, in conferring resistance to invading pathogens, and possibly activities underlying human disease.