Detection of minimal or measurable residual disease (MRD) in acute lymphoid leukemia (ALL) post induction or consolidation has significant prognostic and treatment implications. Persistence of MRD has shown to confer resistance to conventional chemotherapy and predicts for early relapse; therefore, it is regarded as an independent risk factor for poor outcomes. Assessment of MRD through various methods such as multiparameter flow cytometry (MFC), polymerase chain reaction (PCR), or next-generation sequencing (NGS) is important post induction, consolidation, and various other time points in therapy, as indicated, for early therapeutic intervention. Selection of MRD assay depends on its availability and expertise with the method, although each one has its own advantages and disadvantages. Recent development of MRD-directed therapies such as blinatumomab and inotuzumab ozogamicin (InO) has placed significant value on detecting MRD through these methods, as early treatment intervention with these therapies can potentially eradicate MRD and prolong survival. This chapter reviews and compares the different MRD assays, describes the prognostic implications of MRD, and discusses MRD-directed therapies.