Between 15% and 30% of children with acute lymphoblastic leukemia (ALL) experience disease recurrence. With the possible exception of patients presenting with late isolated extramedullary relapse, induction of second complete remission (CR) is employed as a stepping stone to allogeneic hematopoietic stem cell transplantation (HSCT). The authors report their institutional experience in the management of children with recurrent ALL using the Dana Farber Cancer Institute (DFCI) ALL protocol in patients treated initially with that same protocol. Successful reinduction was followed by allogeneic HSCT when possible. Between April 1986 and May 2003, 34 patients with recurrent ALL, treated at initial diagnosis with DFCI-ALL protocol therapy, were given the same protocol as repeat induction chemotherapy. The median age was 4.6 years at diagnosis and 7.1 years at recurrence. Median duration of CR1 was 30.3 months. Second CR was obtained in 29 (85%) patients. Twenty went on to allogeneic HSCT; 10 of them currently remain in CR. Two additional patients treated with chemotherapy without HSCT are also in continuous CR2. Overall, 13 (38%) of the 34 patients are alive with a median follow-up of 105 months. There were no toxic deaths due to the reinduction therapy. One child died of cardiac failure after autologous HSCT. The treatment of children with recurrent ALL using the DFCI-ALL protocol induction regimen after initial use of the same protocol is associated with a high rate of second CR with no excess toxicity. However, the overall prognosis in these patients remains unsatisfactory and needs to be improved.