Objective To review the emerging role of DNA methylation inhibitors in cancer therapy and make a serious reflection on their current status and future perspectives. Data sources The data used in the present article were mainly from PubMed with relevant English papers published from April 1988 to January 2010. The search terms were "DNA methylation", "demethylation" and "cancer". Study selection Studies involed in the DNA methylation in carcinogenesis and DNA methylation inhibitors for cancer therapy were selected. The original milestone articles were also included. Results Treatment with DNA methylation inhibitors leads to demethylation of a panel of tumour suppressor genes and reverse the expression in different tumors, thus making them potential cancer therapeutics. However, we cannot be very optimistic about their future perspectives because we still have a long way to go before they function well like specific targeted anticancer drugs as we expected.Conclusion The best way forward is to further clarify the exact methylation profiles of tumors and to develop novel agents targeting the specific genes.