The quality of maternal and fetal health is a leading predictor of infant well-being that continues into childhood, adolescence, and adulthood. Thus, early diagnosis of pre- and neonatal diseases are of utmost importance for treatment initiation before the disease progresses. Delayed diagnosis often causes developmental retardation and disability. This book will explore the recent clinical and research findings in the field of prenatal/neonatal screening and diagnostics, including molecular and biochemical tests, imaging, and clinical examinations. The advent of noninvasive prenatal testing (NIPT) led to their adoption for screening pregnant mothers for fetal DNA aneuploidies and other chromosomal or genetic abnormalities. A wide variety of highly sensitive molecular assays, that include FISH, MLPA, qPCR, microarray diagnostics, and next-generation sequencing, provide a comprehensive genetic and cytogenomic assessment of the fetus or newborn DNA. Genomics newborn screening (GNS) in neonatal care units has proven to be a life-saving solution. GNS testing program aids in the diagnosis of rare conditions, which allows neonatologists and pediatricians to determine the best patient care possible. Perinatal genetic counseling is now, almost solely, based on the genomics test results that offer parents who are at risk of having offspring with known pathogenic gene variants the option to make informed decisions about current or future pregnancies. Genome editing technologies are now applied as individualized treatment of malfunctioning gene. High-throughput biochemical technologies like mass spectrometry offer tests that can multiplex the detection of several biomarkers for metabolic disorders. These tests become invaluable as a blood spot-based newborn screening test for lysosomal storage disorders and other inborn errors of metabolism. High-complexity diagnostic tests are inevitably accompanied by the generation of big data and the need for complex medical informatics infrastructure. The implementation of these assays into routine clinical practice raises ethical, legal, and social concerns about data storage, security, and patient’s privacy. Additionally, there are limitations to modern testing: in some cases, the genomic test results are difficult to interpret (e.g., detection of genetic variants of uncertain significance). All these elements (as well as the cost and the need for highly qualified healthcare professionals with specialized training) hinder the universal adaptation of high-complexity assays worldwide. These issues will be touched upon in various chapters of the book. The other topics in prenatal and neonatal diagnoses (e.g., mother-fetus transmitted infections, neonatal abstinence syndrome, RhD status diagnosis, audiometric and critical congenital heart disease evaluation) will also be discussed in this book. Novel technologies, detailed in this book, will drive advances in early pre- and neonatal disease diagnoses and the development of novel therapeutic modalities. The ultimate goal is to initiate preventive measures or get the right treatment to the right person at the right time.