A variety of invasive and non-invasive tests have been included in the modern prenatal care. Invasive and diagnostic tests (chorionic villus sampling and amniocentesis) are performed in “high risk” pregnancies, while non-invasive, biochemical or/and ultrasonographical screening tests are available to all pregnant women regardless of their age, in particular to those women who do not have any personal or family history of genetic disorder. The purpose of a prenatal screening test is to identify individuals at a sufficient risk of a specific disorder to benefit from a further diagnostic investigation. Nowadays, the second trimester serum screening for one of the most common autosomal aberrations, trisomy 21 (Down syndrome), has been gaining a wide acceptance. Generally, it is carried out between 15 to 18 weeks of gestational age and the risk evaluation is based on the combination of the maternal agespecific risk for an affected pregnancy together with the risk associated with the concentrations of maternal serum alpha-fetoprotein, human chorionic gonadotropin or its free β-subunit and unconjugated estriol. The second trimester detection rate for Down syndrome is 60-75% at a 5% false positive rate. The first trimester screening for trisomy 21 can be performed using combined measuring of the fetal nuchal translucency thickness and the maternal serum free β-hCG as well as the pregnancy associated plasma protein-A. In this case, a detection rate of 75-90% at a 5% false positive rate can be achieved. In addition to Down syndrome, serum-screening tests are also effective in the detection of neural tube defects, abdominal wall defects, trisomy 18 (Edward’s syndrome), Turner syndrome, Smith-Lemli-Opitz syndrome and steroid sulfatase deficiency.