Unrelated donor cord blood (CB) transplantation (CBT) results in disease-free survival comparable to that of unrelated adult donor transplantation in patients with hematologic malignancies. Extension of allograft access to racial and ethnic minorities, rapid graft availability, flexibility of transplant date, and low risks of disabling chronic graft-versus-host disease (GVHD) and relapse are significant advantages of CBT, and multiple series have reported a low risk of late transplant-related mortality (TRM) post-transplant. Nonetheless, early post-transplant morbidity and TRM and the requirement for intensive early post-transplant management have slowed wide adoption of CBT. Targeted care strategies in CBT recipients can, however, mitigate early transplant complications and reduce transplant costs. Herein, we provide a practical “how to” guide to CBT for hematologic malignancies on behalf of the NMDP and the ASBMT CB Special Interest Group (SIG). It shares the best practices of 6 experienced United States transplant centers with a special interest in the use of CB as a hematopoietic stem cell source. We address donor search and unit selection, unit thaw and infusion, conditioning regimens, immune suppression, management of GVHD, opportunistic infections and other factors in supportive care appropriate for CBT. Meticulous attention to such details has improved CBT outcomes and will facilitate the success of CBT as a platform for future graft manipulations.