Adult acute lymphoblastic leukemia (ALL) is a heterogeneous disease affected by many patient- and disease-related factors, including age, immunologic subtype, and clinical, genetic, and molecular features. Allogeneic hematopoietic cell transplantation (HCT) has occupied an increasing therapeutic role as a result of significant improvements in supportive care and histocompatibility testing. ALL Philadelphia chromosome-negative patients formerly excluded now are considered HCT candidates and survival rates with alternative donors may approach those obtained with matched-related donors. Reduced-intensity conditioning rather than myeloablative conditioning appears to provide comparable patient outcome results although these observations have not been validated in prospective studies. Improved tools can identify patients thought to be in remission based on morphology but who have active disease at the molecular or immunophenotypic level (minimal residual disease). Using B-cell antigen panels, clone-specific immunoglobulins, or T-cell receptor rearrangements to detect positivity at thresholds of at least 1 in 10(4) cells, such patients may be taken to HCT. The ongoing advances in conventional therapy intensity, however, now yield improved results and ongoing reassessment of the place of HCT needs to be continued; every effort should be made to enroll eligible patients in clinical trials.