In the past decade, mesenchymal stem cells (MSC) have received much attention in equine veterinary medicine. The first therapeutic use of equine MSC was reported in 2003. Since then, the clinical application of MSC has been exploding with thousands of horses now treated worldwide. At present, MSC are mainly used in veterinary medicine to treat musculoskeletal diseases based on their ability to differentiate into various tissues of mesodermal origin. This is in marked contrast to human medicine, where MSC therapies are primarily focused on immune-mediated, inflammatory, and ischemic diseases. In this review, both orthopedic as well as non-orthopedic clinical applications of equine MSC are discussed. A brief overview is provided on the potential of MSC for non-orthopedic injuries with emphasis on those diseases, which occur in both humans and horses.