Post-traumatic arthritis is a progressive and debilitating joint disease that commonly occurs following joint trauma, such as ligament injury, meniscal tear, or intra-articular fracture. However, there are few therapeutic approaches currently available that have been shown to alter the course of this disease. Recent studies have shown that several different types of adult stem cells possess regenerative capabilities for a wide range of disease states. In particular, several studies have shown that exogenously delivered stem cells can enhance regeneration and diminish the severity or progression of post-traumatic arthritis. The mechanisms by which these cells act are not fully understood, but appear to involve the secretion of bioactive factors or the alteration of the cytokine and growth factor production of endogenous cells. Here we review the animal studies that have investigated the potential of stem cell therapies for reducing the severity of PTA, as well as some of the potential mechanisms that may be involved in these responses, and the current clinical trials being performed in this area.