Screening is a process of picking up people from a normal population group who are at apparently “high risk” for any condition. So, the results of a screening test are “screen positive”, i.e. “high risk” for a condition or “screen negative”, i.e. “low risk”, which indicates low probability of having that condition. A screening test helps in optimizing the need for invasive testing while increasing the pick-up rate for fetal chromosomal problems (aneuploidies). This chapter covers the first-trimester combined screening test, first-trimester screening blood test, second-trimester maternal serum biochemistry (quadruple test), and noninvasive prenatal testing—cell-free fetal DNA in maternal blood.