Ischemic kidney diseases are common clinical entities that bear high mortality and morbidity and may lead to irreversible loss of kidney function. Their pathophysiology is multifaceted, involves complex hormonal-immunological-cellular interactions, and leads to damage in multiple cell types, which is often resistant to conventional therapy. Thus, novel strategies are needed to repair the renal parenchyma and preserve kidney function. Mesenchymal stem cells (MSC) confer renal protection through paracrine/endocrine effects and to some degree possibly by direct engraftment. Their anti-inflammatory and immune-modulatory properties target multiple cascades in the mechanisms of ischemic kidney disease. This review focuses on recent progress on the use of MSC to prevent kidney injury in ischemic kidney injury, with a focus on the chronic form.