For decades it has been common knowledge that some cells from the developing fetus make their way into maternal circulation, and that this process starts in the early weeks of first trimester. Naturally, when alternative technologies for prenatal diagnosis were being explored, the use of fetal cells for noninvasive prenatal diagnosis came on top of the list. After years of intermediate success and failure, the interest in fetal cells circulating in maternal blood has come full circle. Recent advances in single fetal cell genetic analyses have invigorated interest in fetal cells for prenatal diagnostics. However, for this interest to sustain, we propose a list of best practices that have their origins in the lessons learned from past successes and failures.