The umbilical cord is a noncontroversial source of mesenchymal-like stem cells. Mesenchymal-like cells are found in several tissue compartments of the umbilical cord, placenta, and decidua. Here, we confine ourselves to discussing mesenchymal-like cells derived from Wharton's Jelly, called umbilical cord matrix stem cells (UCMSCs). Work from several laboratories shows that these cells have therapeutic potential, possibly as a substitute cell for bone marrow-derived mesenchymal stem cells for cellular therapy. There have been no head-to-head comparisons between mesenchymal cells derived from different sources for therapy; therefore, their relative utility is not understood. In this chapter, the isolation protocols of the Wharton's Jelly-derived mesenchymal cells are provided as are protocols for their in vitro culturing and storage. The cell culture methods provided will enable basic scientific research on the UCMSCs. Our vision is that both umbilical cord blood and UCMSCs will be commercially collected and stored in the future for preclinical work, public and private banking services, etc. While umbilical cord blood banking standard operating procedures exist, the scenario mentioned above requires clinical-grade UCMSCs. The hurdles that have been identified for the generation of clinical-grade umbilical cord-derived mesenchymal cells are discussed.