Sophisticated screening protocols for genetic abnormalities constitute an important component of current prenatal care, aiming to identify high-risk pregnancies and offer appropriate counseling to parents regarding their options. Definite prenatal diagnosis is only possible by invasive prenatal diagnostic testing (IPDT), mainly including amniocentesis and chorionic villous sampling (CVS). The aim of this comparative review was to summarize and compare the existing recommendations on IPDT from the most influential guidelines. All the reviewed guidelines highlight that IPDT is indicated based on a positive screening test rather than maternal age alone. Other indications arise from medical history and sonography, with significant variations identified between the guidelines. The earlier time for amniocentesis is unequivocally set at ≥15 gestational weeks, whereas for CVS, the earlier limit varies from ≥10 to ≥11 weeks. Certain technical aspects and the overall approach demonstrate significant differences. Periprocedural management regarding Rhesus alloimmunization, virologic status and use of anesthesia or antibiotics are either inconsistent or insufficiently addressed. The synthesis of an evidence-based algorithm for IPDT is of crucial importance to healthcare professionals implicated in prenatal care to avoid unnecessary interventions without compromising optimal prenatal care.