Survival rates for children with acute myeloid leukemia (AML) exceed 60 % when modern, intensified chemotherapeutic regimens and enhanced supportive care measures are employed. Despite well-recognized improvements in outcomes, primary refractory or relapsed pediatric AML yields significant morbidity and mortality, and improved understanding of this obstinate population along with refined treatment protocols are urgently needed. Although a significant number of patients with refractory or relapsed disease will achieve remission, long-term survival rates remain poor, and efforts to identify therapies which will improve OS are under continuous investigation. The current fundamental goal of such investigation is the achievement of as complete a remission as possible without dose-limiting toxicities, and the progression to hematopoietic stem cell transplantation thereafter. In this review the scope of the problem of relapsed and refractory AML as well as current and emerging chemotherapy options will be discussed.