Cardiovascular diseases remain a paramount focus of basic and clinical investigation. They are the leading cause of death in developed countries and their prevalence is increasing in the developing countries. Early detection of the formation and progression of atherosclerotic plaques is therefore essential. Proteomics is a tool designed to address this need at the level of signal transduction, organelle and cellular mechanism and biomarker development. This review examines the increasing use of traditional and novel biomarkers that are transforming cardiovascular medicine.