Massively parallel DNA-sequencing systems provide sequence of huge numbers of different DNA strands at once. These technologies are revolutionizing our understanding in medical genetics, accelerating health-improvement projects, and ushering to a fully understood personalized medicine in near future. Whole-exome sequencing (WES) is application of the next-generation technology to determine the variations of all coding regions, or exons, of known genes. WES provides coverage of more than 95% of the exons, which contains 85% of disease-causing mutations in Mendelian disorders and many disease-predisposing SNPs throughout the genome. The role of more than 150 genes has been distinguished by means of WES, and this statistics is quickly growing. In this review, the impacts of WES in medical genetics as well as its consequences leading to improve health care are summarized.