Umbilical cord blood transplant is an alternative graft source for patients lacking a human leukocyte antigen-matched donor; however, delayed engraftment times have historically resulted in transplant-related morbidity and mortality from complications such as infections and ineffective hematopoiesis. Recent advances in ex vivo expansion techniques have successfully augmented the initial cell dose delivered from an umbilical cord blood graft, leading to improved immune reconstitution, durable hematopoiesis, decreased transplant-related morbidity and mortality, and better outcomes. Herein we review the data for existing and developing ex vivo expansion techniques, with a focus on the preclinical and clinical data for nicotinamide-mediated cord blood expansion across both malignant and benign hematologic indications.