In the era of prenatal ultrasound and biochemical screening and also due to the increase of noninvasive prenatal testing and screening (NIPT, NIPS), invasive prenatal techniques are the most appropriate procedures for diagnosing chromosomal, metabolic, and genetic fetal anomalies. Chorionic villous sampling (CVS) in the first trimester of pregnancy is currently the technique of choice for women at high genetic risk. Amniocentesis is more frequently employed in the second trimester while fetal blood sampling (FBS) by cordocentesis is rarely used nowadays. Women who choose to avoid the termination of pregnancy (TOP) of an affected fetus can opt for preimplantation genetic diagnosis (PGD) by assisted reproductive techniques (ART) by transferring in utero only the microbiopsied non-affected embryos or blastocysts. All invasive prenatal diagnosis procedures are performed under continuous ultrasound monitoring and can be done both free-hand or by insertion of a spinal needle in the ultrasound probe. Chorionic villous sampling can be performed by transcervical or transabdominal route; this last one is preferred mostly because it can be employed in any trimester of pregnancy but also because it is simpler and therefore easier for hands-on training, faster, less invasive; it is also associated with lower risks of infections and fetal loss. In antenatal diagnosis, the first step is non-directive pretest counseling to explain the risks and efficacy and to provide information about the procedures and the disease. The new laboratory analysis techniques are in continuous progress and their efficacy and success are very high for chromosomal anomalies using traditional karyotype by direct analysis of cytotrophoblastic and cultured metaphases of chorionic tissue. Alternatively, quantitative fluorescent polymerase chain reaction (QF-PCR) and array comparative genetic hybridization (aCGH) can be utilized. DNA amplification by PCR and, recently, next-generation sequencing (NGS) have shown high sensitivity and specificity for single-gene diseases. Audit of clinicians and adequate training of fellows are of paramount importance to have the highest quality results. The authors of this manuscript would like to thank Fondazione di Sardegna; Sardinia Regional Department for Programming; Boyana Petrova Tsikalova, MA in English Philology.