Extraosseus calcification has plagued management of renal failure since the beginning of hemodialysis, but the issue has largely been neglected because the impact on survival was thought to be limited. The recent recognition that hyperphosphatemia is a strong predictor of all-cause mortality, and particularly of cardiac mortality, has transformed the situation. Relatively stringent, though difficult to implement, guidelines have been proposed for the management of hyperphosphatemia. Important recent insights document that, for different reasons, both high and low turnover of bone disease increase the risk of vascular calcifications. Vascular calcification impacts cardiac death not only by complicating coronary atherosclerosis, but also by increasing the stiffness of central arteries, impacting on heart function (increased impedance, reduced coronary perfusion). While in the past extraosseous calcification, including vascular calcification, was thought to be a passive process resulting from transgression of a critical Ca x P product, recent studies show that the adverse effect of hyperphosphatemia is also mediated by active processes (e.g., induction of "osteogenic" genetic programs), and is modulated by calcification inhibitors.