The concept of a post-natal "mesenchymal stem cell" ("MSC") originated from studies focused on bone marrow stromal cells (BMSCs), which are non-hematopoietic adherent cells, a subset of which are skeletal stem cells (SSCs), able to form cartilage, bone, hematopoiesis-supportive stroma, and marrow adipocytes based on rigorous clonal and differentiation assays. Subsequently, it was speculated that BMSCs could form other mesodermal derivatives and even cell types from other germ layers. Based on BMSC surface markers, representative of fibroblastic cells, and imprecise differentiation assays, it was further imagined that "MSCs" are ubiquitous and equipotent. However, "MSCs" do not have a common embryonic origin and are not a lineage, but recent studies indicate that they are tissue-specific stem/progenitor cells. These cells share cell surface features owing to their fibroblastic nature, but they are not identical. They display different differentiation capacities based on their tissue origin but do not "trans-differentiate" outside of their lineage, based on rigorous assays. For these reasons, the "MSC" term should be abandoned. Tissue-specific stem/progenitor cells provide the opportunity to devise methods for tissue regeneration by the cells themselves (tissue engineering). Their use in other forms of regenerative medicine based on paracrine, immunosuppressive, and immunomodulatory effects is far less clear.