As an archetype of human adult stem cells that can readily be harvested, enriched and expanded in vitro, mesenchymal stromal cells (MSC) have been reported to be of significance for regenerative medicine. The literature is replete with reports on their developmental potentials in pre-clinical model systems. Different preparative protocols have been shown to yield MSC-like cell cultures or even cell lines, from starting materials as diverse as bone marrow, fat tissue, fetal cord blood and peripheral blood. However, MSC are still ill-defined by physical, phenotypic and functional properties. The quality of preparations from different laboratories varies tremendously and the cell products are notoriously heterogeneous. The source and freshness of the starting material, culture media used, presence of animal sera, cytokines, cell density, number of passages upon culture, etc., all have a significant impact on the (1) cell type components and heterogeneity of the initial population, (2) differential expansion of specific subsets, with different potentials of the end products, and (3) long-term functional fate of MSC as well as other types of progenitor cells that are co-cultivated with them. Consequently, there is an urgent need for the development of reliable reagents, common guidelines and standards for MSC preparations and of precise molecular and cellular markers to define subpopulations with diverse pathways of differentiation and divergent potentials.