Screening for Down syndrome began with the question "How old will you be when you deliver?".  If the pregnant woman answered 35 years of age or older, she was offered amniocentesis and a karyotype (diagnostic testing). Since then, serum markers in the second trimester have been used to form the Quadruple test.  While in the first trimester the ultrasound  and serum markers are identified as the Combined test.  When results from both trimester are used, this is termed the integrated test.  The integrated test has about a 90% detection rate for a 2% false positive rate and was the highest performing test until 2011.  It is important to note that these are phenotypic-based tests.  The finding in 1997 that cfDNA from the feto-placenta unit was in the maternal circulation in a relatively high percentage, allowed for the eventual development of a screening test, once next generation sequencing was available.  It is now clear that cfDNA can detect about 99% of Down syndrome with a false positive rate of 1 or 2 per thousand.  Importantly, this is a genotypic-based test.  Since 2013, cfDNA screening has been routinely used as a secondary screening test in 'high risk' pregnancies.  High detection means that  most of these women will have a negative result and would likely avoid invasive testing.  The low false positive rate means the predictive value will be high.  Current cfDNA screening tests tend to focus on common autosomal aneuploidies, with some expanding coverage to the sex chromosomes.  Recently, laboratories have extending testing to other chromosomes as well as to a limited number of microdeletion syndromes.  However reduced costs and less complexity are needed to allow cfDNA screening to be offered as a first line prenatal test to the entire pregnancy population.  Some tests are now emerging that aim at reducing costs and complexity.  In addition, there are competing methodologies that can identify a broader array of disorders.