The first report of the occurrence of fetal cells in maternal circulation dates back to 1893 when the German pathologist Schmorl identified trophoblast cells in the lungs of women who had died from eclampsia. Till recently, however, the existence of fetal cells in maternal blood was a matter of considerable debate. The main reason for this dispute was the inability to successfully and reliably enrich for these cells, which has also hindered their clinical use. In the meantime, this issue has been addressed and the both fetal aneuploidies and single gene defects can now be detected in a non-invasive manner using fetal cells enriched from maternal blood.