The use of adult stem cells as therapeutic agents to treat disease has become increasingly prevalent. During the last decade, isolated and expanded stem and progenitor cells have demonstrated the capacity to differentiate into multiple cell types. Early optimism that in vitro differentiation capacity would translate into in vivo tissue regeneration has lessened and identifying the mechanisms that underlie the benefit of stem cell repair is an emerging area of investigation. This review considers several of the pathways and mechanisms required for adult stem cell repair. These mechanisms include the mobilization and the homing of stem cells to sites of injury, immunomodulatory effect of stem cells, and the association of stem cells with increased vascularization of injured tissue. These data suggest that the unique properties of adult stem cells can be utilized to treat a wide variety of diseases that cannot be treated with existing pharmacological agents, and prompt new paradigms for the bio-pharmacokinetics of biological expressed by efficacious stem cells.