Hypertension is a major cardiovascular risk factor with a multifactorial pathogenesis, including genetic and environmental factors. In addition to hypothesis-driven strategies, unbiased approaches such as genomics, proteomics, and metabolomics are useful tools to help unravel the pathophysiology of hypertension and associated organ damage. During development of cardiovascular disease the key organs and tissues undergo extensive functional and structural changes that are characterized by alterations in the amount and type of proteins that are expressed. Proteomic approaches study the expression of large numbers of proteins in organs, tissues, cells, and body fluids. A number of different proteomic platforms are available, many of which combine two methods to separate proteins and peptides after an initial digestion step. Identification of these peptides and changes in their expression in parallel with disease processes or medical treatment will help to identify as yet unknown pathophysiological pathways. There is also potential to use proteomic signatures as biomarkers of cardiovascular disease that will contribute to population screening, diagnosis of diseases and their severity, and monitoring of therapeutic interventions.