The pathogenesis of vascular calcifications in uremia is not completely understood, but is regarded as multifactorial, involving traditional and nontraditional risk factors. In particular, derangements in divalent ions are considered of outmost importance, but also the role of physiologic inhibitors of calcification is now claimed. The most powerful physiologic inhibitor of calcification is pyrophosphate, but its biochemical instability precludes its clinical use to date. The pharmacologic analogs of pyrophosphate, bisphosphonates, cannot be easily tested for this purpose in renal patients, given their renal clearance. The list of proteins involved in calcification is a growing one, and experimental models point to the potential clinical relevance of matrix Gla protein, fetuin, osteopontin, osteoprotegerin and bone morphogenetic protein-7. Induction of metabolic acidosis, although theoretically useful, is not recommended, while administration of sodium thiosulphate could be beneficial, but its safety awaits confirmation. Actually, the only available therapies for vascular calcifications are those directed toward achievement of the biochemical targets for calcium, phosphate and parathyroid hormone with the hope, but not the certainty, that this will be efficacious. However, to this purpose, selection of the most appropriate strategy in the individual patient seems essential.