The next decade will focus on identifying the missing heritability of coronary artery disease (CAD). This process will involve a more comprehensive interrogation of common single nucleotide polymorphisms (SNPs) that impart modest biologic effect and an interrogation of rare SNPs that impart profound biologic effect. In parallel, an investigation of the underlying biology of the described association will likely yield novel pathways that provide therapeutic targets. Once we obtain a more complete inventory of sequence variation that predisposes to CAD, a more realistic assessment of the role of genetic risk scoring allied with standard risk algorithms will be possible.