As an organ generally discarded after a normal full-term birth, the placenta is one of the most studied organs from the cellular standpoint. The placenta contains large numbers of immune cells, stem cells, and stromal cells. These cell types spurred the field of regenerative medicine by catalyzing the establishment of cord blood banks and hematopoietic stem cell reconstitution in the treatment of many diseases including cancer. Previously, many scientific articles and reviews have focused on the production, phenotype, and functional characterization of bone marrow-derived mesenchymal stromal cells. In this chapter, the focus will be solely on the biology, phenotype, and functional characterization of placentaderived stromal cells. Modulation of the immune response, including T cell proliferation, dendritic cell maturation, and monocyte differentiation by placenta-derived stromal cells, will be discussed. This chapter will span in vitro functional analyses, animal models highlighting the in vitro data culminating in a summary of current clinical activity.