INTRODUCTION: The clinical application of immunotherapy has resulted into a significant improvement in the outcome of children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL). In this setting, the use of bispecific T-cell-engager antibodies (BiTEs), such as blinatumomab, which harness the cytotoxic activity of T cells against CD19-positive lymphoblasts, has emerged as a most promising and impactful strategy. Areas covered: This review discusses the main structural and functional features of BiTEs, as well as the current status of their clinical application in childhood ALL. Moreover, future prospects to increase the efficacy of BiTEs are addressed. Expert commentary: The promising results obtained in patients with advanced BCP-ALL pave the way for further improvement in the context of less resistant/advanced disease. Future research is rapidly progressing on several aspects, including the use of blinatumomab in first-line protocols, identification of factors predicting response, use of combinatorial approaches and bioengineering of new molecules with dual specificity or increased potency, stability and half-life. The results of these studies, expected to be available in the next future, will provide further advancement in the development of effective, impactful, targeted immunotherapy for treatment of childhood BCP-ALL, with the concrete potential to revolutionize the clinical practice.