Mesenchymal stem cells (MSCs) have been isolated from bone marrow, periosteum, trabecular bone, adipose tissue, synovium, skeletal muscle and deciduous teeth. These cells have the capacity to differentiate into cells of connective tissue lineages, including bone, fat, cartilage and muscle. A great deal has been learned in recent years about the isolation and characterization of MSCs, and control of their differentiation. These cells have generated a great deal of interest because of their potential use in regenerative medicine and tissue engineering and there are some dramatic examples, derived from both pre-clinical and clinical studies, that illustrate their therapeutic value. This review summarizes recent findings regarding the potential clinical use of MSCs in cardiovascular, neural and orthopaedic applications. As new methods are developed, there are several aspects to the implanted cell-host interaction that need to be addressed before we can fully understand the underlying mechanisms. These include the host immune response to implanted cells, the homing mechanisms that guide delivered cells to a site of injury and the differentiation in vivo of implanted cells under the influence of local signals.