Heart disease is a leading cause of death in the United States, and hypertension is a predominant risk factor. Thus, effective blood pressure control is important to prevent adverse sequelae of hypertension, including heart failure, coronary artery disease, atrial fibrillation, and ischemic stroke. Over half of Americans have uncontrolled blood pressure, which may in part be explained by interpatient variability in drug response secondary to genetic polymorphism. As such, pharmacogenetic testing may be a supplementary tool to guide treatment. This review highlights the pharmacogenetics of antihypertensive response and response to drugs that treat adverse hypertension-related sequelae, particularly coronary artery disease and atrial fibrillation. While pharmacogenetic evidence may be more robust for the latter with respect to clinical implementation, there is increasing evidence of genetic variants that may help predict antihypertensive response. However, additional research and validation are needed before clinical implementation guidelines for antihypertensive therapy can become a reality.