Cardiovascular disease is the first cause of morbidity and mortality in dialysis patients. Hyperphosphatemia and elevated serum calcium-phosphate levels have recently been investigated as inducing factors on extraskeletal calcification in this population. In vitro studies demonstrated that human aortic smooth muscle cells calcify when incubated in a high phosphate medium, where calcium and calcitriol are not changed. Furthermore, the lack of inhibitory proteins, such as fetuin and matrix Gla protein, is a possible main determinant of calcium-phosphate deposition in soft tissues. The classical treatment of hyperphosphatemia and secondary hyperparathyroidism in dialysis patients consists of calcium-based phosphate binders and calcitriol administration. Unfortunately, this "first-generation" therapy is not free of dramatic side effects. New free-calcium and -aluminum phosphate binders, new vitamin D metabolites, and calcimimetics are examples of "second-generation" therapies that may prevent vascular calcification and possibly prevent some of the burden of cardiovascular disease in uremia.