Fetal cells have been successfully detected in maternal blood in all three trimesters of gestation in a substantial proportion of normal pregnancies. Various enrichment techniques have been developed for fetal trophoblast cells, leucocytes and nucleated red blood cells. Nucleated red blood cells are considered to be best suited for noninvasive prenatal diagnosis. Fluorescence in-situ hybridization detected the first cases of fetal trisomy in maternal blood after enrichment of fetal nucleated red blood cells. Despite recent encouraging results, accurate and reproducible diagnoses of fetal anomalies by polymerase chain reaction or fluorescence in-situ hybridization require further optimization of enrichment devices and detection protocols.