Phosphate binders represent a common intervention in renal patients affected by chronic kidney disease and mineral bone disorder (CKD-MBD). Although counteracting P overload through binders adoption is argued by a physiology-driven approach, the efficacy of this intervention on hard endpoints remains poorly evident. The inconsistencies between rationale and methodological weakness, concerning the clinical relevance of P binding in chronic kidney disease, will be herein discussed with special focus on the need of a multi-factorial treatment against CKD-MBD, which is currently more achievable due to the variety of P binders and the rapid evolution of nutritional therapy, dialysis techniques and nursing science.