Adult stem cell populations selected for use in cardiovascular clinical trials typically are mononuclear cell fractions of bone marrow and peripheral blood or cells of specific cell lineages selected by surface markers such as CD34 or CD133. This article describes a potent stem and progenitor cell population identified by an intracellular marker of “stemness” that crosses multiple lineages. Aldehyde dehydrogenase (ALDH)–bright (ALDHbr) populations isolated from bone marrow contain potent stem and progenitor cells representing all cell types thought to be needed for ischemic repair and include hematopoietic, endothelial, mesenchymal, and neural progenitor cells. An animal model of hindlimb ischemia demonstrated that the ALDHbr population was highly effective in restoring blood flow to ischemic limbs. Based upon the accumulating evidence for a potential therapeutic effect of bone marrow–derived cells in ischemic disease in humans and the vascular regenerative potential of ALDHbr cells in the hindlimb model, clinical trials to investigate the use of autologous bone marrow–derived ALDHbr cells in patients with ischemic heart failure and critical limb ischemia were initiated. Study designs are described. Results of the completed study in patients with critical limb ischemia (CLI) are encouraging and are summarized. Results of 6-month follow-up for the study in ischemic heart failure are pending.