The primary prevention of cardiovascular disease relies on the ability to identify at-risk individuals long before the development of overt events. In the past decade, research into circulating, genetic and imaging biomarkers to augment traditional methods of risk prediction has only achieved modest success. Emerging technologies in the fields of genomics, metabolomics and proteomics are providing new platforms for biomarker discovery. Here, we review current concepts in the evaluation and discovery of cardiovascular biomarkers. Further research is needed to identify new biomarkers to successfully stratify risk of cardiovascular disease in low-risk populations, as well as to test whether management strategies informed by biomarker testing are better than standard of care.