This chapter covers through case studies minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) patients. The persistence of circulating or bone marrow blasts after a multi-agent chemotherapy regimen confers an adverse outcome in adult ALL. Multiparameter flow cytometry (MFC) can be used to detect three different leukemia-associated immunophenotypes, and PCR accurately measures MRD by detecting the genetic aberration that is present in one copy per cell. If no suitable methods for measuring MRD are available for a particular case, one can consider day 7 circulating blasts as a surrogate for MRD and outcome prediction. Persistence of MRD after chemotherapy is associated with clinical relapse in a median of 4–5 months: the 3-year relapse rate among those who had MRD less than 0.01% was zero, whereas the relapse rate among those who had MRD greater than 0.01% was 94%, which suggests that patients who have MRD following chemotherapy should undergo allogeneic SCT. Achieving MRD negativity prior to allogeneic SCT may improve SCT outcome. The addition of other therapies, such as imatinib, to convention chemotherapy has improved the outcome for patients with BCR–ABL-positive ALL. The timing of measuring MRD is not yet standardized.