Microchimerism, the stable persistence of an allogeneic cell population, can result from allogeneic exposures including blood transfusion. Transfusion-associated microchimerism (TA-MC) appears to be a common but newly recognized complication of blood transfusion. Thus far TA-MC has been detected when severely injured patients are transfused. Injury induces an immunosuppressive and inflammatory milieu in which fresh blood products with replication-competent leukocytes can sometimes cause TA-MC. TA-MC is present in approximately half of transfused severely injured patients at hospital discharge and is not affected by leukoreduction. In approximately 10% of patients, the chimerism from a single blood donor may increase in magnitude over months to years, reaching as much as 2% to 5% of all circulating leukocytes. In this review, we discuss recent studies of TA-MC in the civilian trauma population and the potential for study of TA-MC in the military population, where the severity of injury and freshness of blood products suggest that TA-MC may be even more prominent. We also discuss the need for future studies to address the immunology of TA-MC, its stem cell biology, and its clinical manifestations that have the potential to be either pathologic (autoimmunity, graft-versus-host disease) or therapeutic (tolerance induction, various cell and gene therapies).