Structural fetal anomalies complicate up to 5% of pregnancies and an underlying chromosomal or genetic etiology underlies up to half of cases. Understanding the fetal genome is increasingly key in attempting to make a prenatal diagnosis and in delineating a prognosis for the baby. Over the past decades, the field of prenatal genomics has advanced exponentially, beginning with the conventional ‘full’ karyotype available in the 1960s and going up to the present day and beyond with the application of next-generation sequencing (NGS) (Figure 4.1). Current and potential future advances in prenatal diagnostics will allow couples to make more informed decisions prospectively about their pregnancies in addition to aiding decisions on and the development of fetal therapies [1]. In the wake of advancing technologies and large prospective studies such as the United Kingdom’s ‘proof of principle’ 100 000 Genomes Project [2] and the Prenatal Assessment of Genomes and Exomes (PAGE) study [3], the degree of information obtained and turnaround time of results with the development of more sophisticated bioinformatic analytical pathways is likely to improve rapidly. Fetal medicine subspecialists, obstetricians, pediatricians, geneticists, genomic scientists and genetic counselors have a responsibility to stay up to date with this wealth of advances so that couples can be informed accordingly.