In earlier days, periarticular accumulations of calcium phosphate causing tumor-like depositions were considered the result of passive precipitation and referred to as metastatic calcifications. From sophisticated computer tomographic studies and growing insight, we have learned that calcifications in the cardiovascular system are far more threatening and in fact one of the most important sequela of end-stage renal disease. The histologic characteristic of uremia-related calcification is arteriosclerosis of the media. In addition, there is atherosclerosis of the intima, due to the high prevalence of classic cardiovascular risk factors in renal disease. The two vascular features can frequently exist at different sites in the vasculature. Novel diagnostic techniques are helping to elucidate the pathogenetic mechanisms of active conversion of vascular smooth muscle cells to osteochondritic cells. Through this process, extensive calcification of the central and peripheral vasculature ensues, influenced by different promotors and inhibitors. Calciphylaxis is a special form of extraosseous calcification leading to skin necrosis. The factors that trigger the development of calciphylaxis are not completely understood, but this syndrome shares part of the pathophysiologic basis of extraosseous calcification in general. However, the therapeutic approach must be prompt and aggressive, because of the poor prognosis. Frequently, a fatal outcome cannot be avoided in calciphylaxis.