The recovery of fetal cells from the maternal circulation represents a promising approach to noninvasive prenatal diagnosis. Advances in techniques of sensitive molecular genetic analysis have enabled the conclusive demonstration of the presence of fetal cells in maternal blood. In most pregnancies, there are few fetal cells detectable. In some abnormal pregnancies, there appears to be increased fetomaternal transfusion, which facilitates recognition of aneuploid fetal cells. This review article describes general strategies of fetal cell isolation, current technical challenges, and clinical applications that are envisioned for the future. The increased appreciation of fetal cell microchimerism, and its association with complications of pregnancy and the postpartum development of autoimmune disease, is also discussed.