Hematopoietic stem cells (HSCs) have innate ability to remain in the dormant state till they receive molecular cues from the signaling molecules within their niche. Controlling the interaction between stem cells and their niche would offer an opportunity to manipulate stem cell proliferation and differentiation for therapeutic application. There has been immense interest in umbilical cord blood (UCB) as an important source of HSCs to treat malignant and metabolic disorders; as HSCs acquired from UCB have higher proliferative efficacy and longer telomeres than other somatic stem cells. The monograph focuses on the different stem cell niches, their components, signaling molecules, factors controlling the stem cell self-renewal and differentiation. It further recapitulates the current state of umbilical cord transplantation and critically dwells into both the advantages and limitations associated with it. The strategies involved in surmounting the immunological shortcomings and translating the improvisations of stem cell niche for the better clinical outcomes are the salient points of the monograph.