Abstract Arterial calcifications as found with various imaging techniques, like plain X-ray, computed tomography or ultrasound are associated with increased cardiovascular risk. The prevalence of arterial calcification increases with age and is stimulated by several common cardiovascular risk factors. In this review the clinical importance of arterial calcification and the currently known proteins involved are discussed. Arterial calcification is the result of a complex interplay between stimulating (Bone Morphogenetic Protein type 2, RANKL) and inhibitory (Matrix Gla Protein, Bone Morphogenetic Protein type 7, Osteoprotegerin, Fetuin-A, Osteopontin) proteins. Vascular calcification is especially prevalent and related to adverse outcome in subjects with renal insufficiency and diabetes mellitus. We address the special circumstances and mechanisms in these patient groups. Treatment and prevention of arterial calcification is possible by the use of specific drugs. However, it remains to be proven that reduction of vascular calcification in itself leads to a reduced cardiovascular risk.