Sevelamer (Renagel and Renvela), is an orally administered weakly basic anion exchange resin that binds dietary phosphate in the gastrointestinal tract, and is approved for use in the US, Europe and many other countries for the treatment of hyperphosphatemia in adult patients on hemodialysis or peritoneal dialysis. Clinical evidence shows that sevelamer is at least as effective as calcium-based oral phosphate binders in controlling serum phosphate, but with a lower incidence of hypercalcemia. Whilst sevelamer hydrochloride is associated with mild acidosis, sevelamer carbonate does not have this drawback. Use of sevelamer and avoidance of calcium-based binders may slow the progression of vascular calcification in hemodialysis patients, and it also reduces serum low-density lipoprotein-cholesterol levels. There was no between-group difference in all-cause mortality between sevelamer and calcium-based phosphate binder therapy in the primary efficacy analysis of the large (n >2100), 3-year DCOR trial. In the smaller (n = 109) nonblind RIND trial in patients new to hemodialysis, data suggest there may be an overall survival benefit with sevelamer versus calcium-based phosphate binder treatment but the evidence on the efficacy of sevelamer in reducing mortality and hospitalization is not strong. The balance of evidence, however, does not strongly support the use of sevelamer over the much less costly calcium-based binders except in patients at risk of hypercalcemic episodes. Further research into cardiovascular and all-cause mortality over a longer time period would be needed to settle this issue, and the relative survival benefits and cost effectiveness of all phosphate binder therapies remains to be fully determined. Despite the relative paucity of data available, sevelamer has established itself as the most widely used binder in the United States and the most widely used noncalcium-based binder worldwide. However, affordability is a major issue for most health economies and in the light of recent economic events is likely to become more prominent.