Hyperphosphatemia is a major cause of morbidity and mortality in patients with chronic kidney disease. The association between hyperphosphatemia and increased risk of death from cardiovascular disease/vascular calcification has been well established for a long time. This review explores the new aspects of pathogenesis of vascular calcification, as demonstrated by recent advances showing a recognized regulating role of phosphorus in vascular smooth muscle cell calcification. This novel mechanism may help in finding a new pharmacological therapy to reduce, or prevent blood vessel calcification. Furthermore, recent experimental and clinical studies involved in the treatment of hyperphosphatemia are reviewed in this article.