It is now known that cells traffic between fetus and mother during normal human pregnancy. Moreover, fetal cells have been found to persist in the maternal peripheral blood for decades after childbirth. Chronic graft-versus-host disease, a known condition of chimerism that occurs after allogeneic hematopoietic stem cell transplantation has clinical similarities to some autoimmune diseases, including scleroderma (SSc). SSc has a predilection for women and an increased incidence in women following childbearing years. These observations when considered together with the longterm persistence of fetal cells led to the hypothesis that microchimerism is involved in autoimmune diseases such as SSc. Initial studies of women with SSc lend support to the hypothesis. Microchimerism, however, is also very common in healthy normals, and available data is not sufficient to be conclusive with respect to disease pathogenesis. Microchimerism can also occur due to engraftment from a blood transfusion, from a twin, or from the mother, sources that are applicable to men and women who have never been pregnant. The mechanism(s) by which microchimerism might contribute to SSc are not known, although some insight may be gained from studies of chimerism in transplantation biology. If microchimerism does contribute to the pathogenesis of autoimmune disorders such as SSc, it is likely that new therapeutic strategies could be developed.