Cardiovascular disease (CD) and peripheral vascular disease (PVD) are leading causes of mortality and morbidity in western countries and also responsible of a huge burden in terms of disability, functional decline, and healthcare costs. Biomarkers are measurable biological elements that reflect particular physiological or pathological states or predisposition towards diseases and they are currently widely studied in medicine and especially in CD. In this context, biomarkers can also be used to assess the severity or the evolution of several diseases, as well as the effectiveness of particular therapies. Genomics, transcriptomics, and proteomics have opened new windows on disease phenomena and may permit in the next future an effective development of novel diagnostic and prognostic medicine in order to better prevent or treat CD. This review will consider the current evidence of novel biomarkers with clear implications in the improvement of risk assessment, prevention strategies, and medical decision making in the field of CD.