In the past few years, intensive research in the understanding of the biologic characteristics of the mesenchymal stromal cells has already led to some early clinical applications. The aim of this review is to summarize the latest information from basic science advances and the outcome of their use in clinical practice with a particular focus in pediatric patients. The minimum criteria required to identify mesenchymal stromal cells, their immunosuppressive-nonimmunogenic properties and their attribution in the treatment of graft-versus-host disease, in the acceleration of hematopoietic recovery, in tissue repair/tissue engineering and in the treatment of selected inherited disorders are discussed. Appropriate preclinical models, completion of ongoing and development of new clinical trials will establish the role of these cells in the treatment of both adult and pediatric patients.