Mesenchymal stem cells (MSCs) represent a heterogeneous progenitor cell population derived from various sources, including bone marrow, placental and adipose tissues. These cell populations are being extensively investigated for their regenerative, immunomodulatory and tissue-protective properties, and the therapeutic potential of MSCs is officially being tested in patients suffering from ischaemic, inflammatory, autoimmune and degenerative disorders. Unofficially, hundreds of centres worldwide already offer MSCs as a 'miracle' panacea treatment for almost every known human disease. Data from in vitro and animal models suggest that MSCs administered either locally or systemically are able to home to stressed tissue and indeed deliver a protective effect via predominately paracrine factors. Furthermore, dozens of published uncontrolled clinical trials have demonstrated strikingly positive therapeutic effects of MSCs with little acute toxicity; however, no prospective controlled trials have yet confirmed these findings, with the exception of one randomized controlled trial in renal transplantation. Thus, large prospective controlled trials are urgently needed to better understand MSC-based therapies and define their potential utility in the treatment of rheumatic diseases. Herein, I provide my opinions regarding the progress of MSC therapies to date and highlight issues that need to be addressed in the future.