All-trans retinoic acid (ATRA) is very effective in newly diagnosed acute promyelocytic leukemia (APL), yielding remission (CR) rates of 80 to 90%. However, it is associated with a rapid rise in WBC in some patients, with potentially fatal ATRA syndrome. Furthermore, most patients relapse with maintenance therapy using ATRA alone or low-dose chemotherapy. The French APL group thus designed a treatment approach with ATRA followed by intensive chemotherapy. The latter was administered after CR achievement with ATRA, or was rapidly added to ATRA in the case of rapid rise in leukocyte counts. This combined approach, in a pilot study and in a randomized trial, proved superior to intensive chemotherapy alone, by slightly increasing the CR rate but more importantly by reducing the relapse rate. The French group (and other European groups) are now testing in a new randomized trial the better timing of ATRA and chemotherapy administration (ATRA followed by chemotherapy or ATRA plus chemotherapy), and the role (after an intensive consolidation) of maintenance treatment with intermittent ATRA, continuous low-dose chemotherapy, or both.