The maternal peripheral blood circulation can serve as a source of fetal ce
lls for the prenatal diagnosis of genetic abnormalities, eliminating the ne
ed for fetal cell sampling by invasive techniques. However, the extreme sca
rcity of these cells leads to a variety of biological questions and technic
al hurdles on the way to a clinical test. On the biological side, we need t
o know the numbers of fetal cells, their distinguishing properties, and the
variables that affect these properties. On the technical side, we need to
identify fetal cells and maximize both yield and purity of the isolation pr
ocedure. Here we review the questions and challenges as they present themse
lves in our specific approach to the fetal cell isolation project. We also
briefly discuss the question of whether these cells could help to diagnose
fetal infections.