The discovery of the specific PML-RAR alpha gene rearrangement in acute promyelocytic leukemia (APL) and of the in vitro and in vivo differentiation of APL blasts by all transretinoic acid have allowed important advances in the pathophysiology and treatment APL. With a therapeutic strategy combining ATRA and anthracycline-AraC chemotherapy, about 70% of newly diagnosed APL cases can now be cured. ATRA syndrome--the major side effect of ATRA treatment--should, however, be prevented. Reverse transcription polymerase chain reaction of the PML-RAR alpha rearrangement is useful for the monitoring of minimal residual disease. Efforts are currently being made to treat patients that relapse and become resistant to ATRA.