Cytosine deaminases of the AID/APOBEC family have a weighty influence on human health. These enzymes are part of the innate and humoral immunity; they participate in lipid metabolism and muscle development, protect cells from viruses and regulate retrotransposition. If the activity of AID/APOBEC deaminases is misregulated, they can become “weapons of mass destruction,” causing deaminations in unprotected single-stranded DNA regions leading to genome-wide mutagenesis. Ultimately, mutations contribute to cell malignancy and rapid evolution of cancer cells, helping them to evade the organism’s defense. Also, hypermutable tumor cells develop resistance to anti-cancer drugs. Here we overview current understanding of the structure, functions, and regulation of AID/APOBEC cytosine deaminases in connection to carcinogenesis.