There are numerous genetic disorders that affect sodium, potassium, and chloride homeostasis. Sodium is the most extensively studied electrolyte because of its association with the salt-sensitive phenotype and the role it has with hypertension. Many genes have been identified and investigated because of the resulting benefits of identifying the salt-sensitive phenotype in clinical practice. There is great potential to tailor dietary and pharmacological interventions based on whether individuals are sensitive or resistant to salt. While further research is needed to clarify this relationship, there are promising genetic variants that have been identified to predict this phenotype. As heart disease is one of the top public health burdens in the United States, identifying more effective treatment strategies in this therapeutic area is greatly needed and utilizing the salt-sensitive classification is one approach.