The conclusion of the Human Genome Project (HGP) in 2003 inspired analysis of the genetic underpinnings of intellectual and developmental disorders (ID/DD), and massive efforts have been made to lower the cost and time required to sequence entire genomes while simultaneously increasing efficiency and accuracy. Genome sequencing is now considered a reliable research and diagnostic tool, ushering in an era of big data in genetic research. Today, large genomic datasets are uploaded into online databases for rapid global sharing. Clinically relevant comparisons are now possible, and the molecular pathogenesis of both common and rare ID/DD can be elucidated. This entry offers a brief overview of whole genome sequencing (WGS) and whole exome sequencing (WES) and their applications in ID/DD research and treatment.