Traditional risk factors for atherosclerotic cardiovascular disease (CVD) do not adequately explain the considerable increase in cardiovascular mortality observed among patients with end-stage renal disease (ESRD): these patients experience mortality rates 10-100 times those without ESRD. Disorders of mineral metabolism, including abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D, represent cardiovascular risk factors unique to the ESRD population. These disturbances manifest clinically through the promotion of extraskeletal calcification and disorders of bone remodeling, two processes which appear to share a common pathogenesis. This article presents evidence describing the impact of calcification-induced arterial stiffness on cardiovascular outcomes of patients with ESRD, along with data relating altered mineral metabolism to all-cause and cardiovascular mortality. Specific management recommendations include 1) early intervention to prevent the development of overt secondary hyperparathyroidism, 2) a more judicious strategy for vitamin D therapy, and 3) a thoughtful approach to the use of calcium-containing phosphate binders, taking into account the underlying bone remodeling disorder and the presence or absence of extraskeletal calcium accumulation.