The pharmacological inhibition of DNA methyltransferases provides novel opportunities for the therapy of human cancers. Several Phase III trials of DNA methyltransferase inhibitors have been completed successfully, but the efficacy of these compounds appears to be compromised by their lack of specificity. To address this issue, much work has been focused on defining the functional characteristics of human DNA methyltransferases. This knowledge will be essential for the design of a new generation of pharmacological inhibitors that target epigenetic processes.