Hyperphosphatemia is a characteristic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Phosphorus excess is an independent risk factor for cardiovascular morbidity and mortality in patients with advanced CKD. The keystones of hyperphosphatemia treatment are reduction of dietary phosphorus, use of phosphate binders, and optimized phosphorus removal via dialysis. Several phosphate binders have been approved for use; all share a common functionality in that they bind phosphorus and reduce the amount absorbed in the gastrointestinal lumen. In the past, treatment with oral phosphate binders was intended to prevent symptomatic secondary hyperparathyroidism. More recently, achieving tighter control of markers associated with abnormal mineral metabolism has become a specific therapeutic objective. This therapeutic shift has been driven by several factors: observational data that link disordered mineral metabolism with adverse clinical outcomes; concern about vascular calcification, which is also associated with adverse outcomes and may correlate with exposure to calcium-based phosphatebinding agents; and, perhaps, the availability of new therapeutic agents. In this article we review the rationale for treatment with oral phosphate binders, discuss evidence that supports the use of the available agents, and suggest an approach for clinical practice.