Although the outcomes for adults with acute lymphoblastic leukemia (ALL) lag behind the stunningly successful results seen in children, new paradigms and new discoveries bring hope that this disparity will steadily lessen. The adoption of the use of pediatric intensity-type regimens in adolescents and young adults show promise in improving outcomes in this population. Recent donor-versus-no-donor comparisons in the allogeneic transplant setting highlight a potent graft-versus-leukemia effect in ALL, and the application of reduced intensity conditioning transplants may exploit this effect while reducing nonrelapse mortality. New therapeutic targets, such as CD22 in precusor B-cell ALL and mutations in NOTCH1 in T-cell ALL, are being exploited in clinical trials. Finally, use of molecular techniques and flow cytometry to quantitate minimal residual disease will allow further stratifications of patients by risk, identification of new therapeutic targets and will lessen drug toxicity through the use of pharmacogenomics.