The human genome contains approximately 3.2 billion nucleotides and about 23,500 genes. Each gene has protein-coding regions that are referred to as exons. The human genome contains about 180,000 exons, which are collectively called an exome. An exome comprises about 1% of the human genome and hence is about 30 million nucleotides in size. Today’s technologies afford the opportunity to sequence all nucleotides in the human exome and even in the human genome. Given that more than three-quarters of the known disease-causing variants are located in the exome, and considering the cost and technical challenges in analyzing the whole genome sequence data, the focus of present research is primarily on whole exome sequencing (WES). While WES at the medical sequencing level is still expensive, it is becoming more affordable. Cost will not likely be a major barrier in the near future, and the data analysis is becoming less tedious. The most difficult challenge at the heart of medical sequencing is interpreting the findings. Each exome contains about 13,500 single nucleotide variants (SNVs) that affect the amino acid sequence, and a large number are expected to be functional variants. The daunting task is to distinguish the variants that are pathogenic from those that have minimal or no discernible clinical effects. While various algorithms exist, none are sufficiently robust. Thus, in-depth knowledge in genetics and medicine is essential for the proper interpretation of the WES findings. This review will discuss the potential applications of the WES data in the practice of cardiovascular medicine.