Context: The number of adults with osteoarthritis in the United States is expected to nearly double from 21.4 million in 2005 to 41.1 million by 2030. As a result, medical costs and associated comorbidity will exponentially increase in the coming decades. In the past decade, mesenchymal stem cells (MSCs) have emerged as a novel treatment for degenerative joint disease. Evidence Acquisition: PubMed (from 1990 to 2013) was searched to identify relevant studies. Reference lists of included studies were also reviewed. Study Design: Clinical review. Level of Evidence: Level 3. Results: We identified 9 animal and 7 human studies investigating the use of MSCs in the treatment of osteoarthritis, with varying levels of support for this therapy. Conclusion: While MSCs have shown potential for improving function and decreasing inflammation in animal studies, translation to patients is still in question. There is a great deal of heterogeneity in treatment methods. Standardizing the manufacturing and characterization of MSCs will allow for better comparisons.