Decitabine (Dacogen(®), Eisai Inc., NJ, USA) is a nucleoside analogue DNA methyltransferase inhibitor first synthesized and documented to have antileukemic efficacy over 40 years ago. Over the years, the dosing of decitabine has been refined, such that for acute myeloid leukemia, a 5-day schedule of 20 mg/m(2) is now commonly utilized. Owing to its relatively modest nonhematologic toxicity when administered in this manner, single agent decitabine has shown the greatest promise in antileukemic efficacy for the management of older individuals and others who are not candidates for more intensive therapy. Whether or not single-agent decitabine is more safe and effective than existing therapies for older individuals, which markers best predict for response, and what drugs combine most effectively with decitabine, are all areas of active investigation at this time.