Over the past 5 years, adult pluripotent stem cell lines have been isolated from multiple organs and tissues in laboratories worldwide. Adult pluripotent stem cells are capable of regenerating tissues of all three primitive germ layers and express pluripotency markers, such as Oct4 or telomerase, which are associated with the primitive stem cell properties of embryonic stem cells. As our collective understanding of the biology of these unique cells has improved, so has our ability to isolate, expand and subsequently evaluate them as therapeutics in preclinical models of acute injury and disease. Pluripotent adult stem cells, as opposed to tissue-restricted adult stem cells, such as mesenchymal stromal cells; have extensive replicative capacity enabling large-scale clinical expansion. This is essential to achieving consistent clinical response data and enabling the cost-effective production necessary for commercial adoption. In addition, investigators have reported effective use of allogeneic adult pluripotent stem cells in acute ischemic injury models in the heart and brain, supporting the 'off the shelf' product concept for this cellular therapy. In this article, the authors review preclinical animal data demonstrating the benefit of pluripotent adult progenitor cells in the treatment of ischemic injuries of the heart, vascular system and CNS.