Recent studies indicate cell traffic occurs between the fetus and mother during pregnancy and that low numbers of fetal cells commonly persist in the maternal circulation for years thereafter. Microchimerism refers to a small number of cells or DNA from one individual harbored in another individual. Autoimmune diseases are more common among women and often increase in incidence following reproductive years. Chronic graft vs. host disease is an iatrogenic form of chimerism with similarities to some autoimmune diseases for which the HLA relationship of donor and host are of central importance. When considered together, these observations led to the hypothesis that microchimerism and HLA relationships of host and non-host cells are involved in autoimmune disease. The hypothesis is applicable to men, children and women without pregnancies because there are other sources of microchimerism, including from a twin, the mother or a blood transfusion. Microchimerism has now been investigated in a number of different diseases with some results supporting a potential role in disease pathogenesis. However, fetal and maternal microchimerism are also found in organs affected by non-autoimmune conditions. Moreover, microchimerism is commonly detected in the peripheral blood of healthy individuals raising the intriguing question of whether these cells are simple remnants of pregnancy or whether they might also have beneficial effects for the host.