Mesenchymal stem cells (MSCs) have become one of the most studied stem cells, especially toward the healing of diseased and damaged tissues and organs. MSCs can be readily isolated from a number of adult tissues by means of minimally invasive approaches. MSCs are capable of self-replication to many passages and, therefore, can potentially be expanded to sufficient numbers for tissue and organ regeneration. MSCs are able to differentiate into multiple cell lineages that resemble osteoblasts, chondrocytes, myoblasts, adipocytes, and fibroblasts and express some of the key markers typical of endothelial cells, neuron-like cells, and cardiomyocytes. MSCs have been used alone for cell delivery or seeded in biomaterial scaffolds toward the healing of tissue and organ defects. After an increasing number of the "proof of concept" studies, the remaining tasks are many, such as to determine MSC interactions with host cells and signaling molecules, to investigate the interplay between MSCs and biological scaffold materials, and to apply MSC-based therapies toward clinically relevant defect models. The ultimate goal of MSC-based therapies has valid biological rationale in that clusters of MSCs differentiate to form virtually all connective tissue during development. MSC-based therapies can only be realized our improved understanding of not only their fundamental properties such as population doubling and differentiation pathways but also translational studies that use MSCs in the de novo formation and/or regeneration of diseased or damaged tissues and organs.