While the world of genetics has been dominated over the last decade by technological advances allowing the identification of common variants underlying the major complex diseases, it is increasingly clear that other genetic mechanisms are also involved in genetic susceptibility and resistance to disease. One understudied contender is microchimerism (maternal and foetal), resulting from bi-directional transfer of cells across the placental barrier in pregnancy. Data from several diseases suggest that elevated levels of microchimerism are associated with autoimmunity. Theories differ however on the role of these cells in the disease process. Some suggest that they increase genetic susceptibility while others suggest that these cells are effectors of the immune response, or that they represent the target of the immune response while another proposes that elevated levels in disease are caused by ongoing repair of damaged tissue. Intriguingly these semi allogeneic cells are tolerated in healthy individuals, albeit at a lower level than in disease scenarios and recent studies in cancer suggest that foetal microchimeric cells may provide surveillance and repair. Many questions remain to be answered about this new avenue of genetics. It is likely that as technology advances our understanding of, and ability to manipulate these cells for therapeutic gain, will push forward new frontiers in medicine.