End stage liver disease is responsible for 30,000 deaths per year in the US alone, and is continuing to increase every year. With liver transplantation the only curative treatment currently available, new therapies are in great demand. Mesenchymal Stem Cells (MSC) offer an opportunity to both treat liver inflammatory damage as well as reverse some of the changes that occur following chronic liver injury. With the ability to regulate both the innate and adaptive immune system, as well as both inhibit and promote apoptosis of effector inflammatory cells, there are numerous therapeutic opportunities for MSC in acute and chronic liver disease. This article critically appraises the potential roles of MSC in liver disease, as well as the barriers to their adoption into clinical practice.