Phosphate handling in the body is complex and involves hormones produced by the bone, the parathyroid gland and the kidneys. Phosphate is mostly found in hydroxyapatite. however recent evidence suggests that phosphate is also a signalling molecule associated with bone formation. Phosphate balance requires careful regulation of gut and kidney phosphate transporters, SLC34 transporter family, but phosphate signalling in osteoblasts and vascular smooth muscle cells is likely mediated by the SLC20 transporter family (PiT1 and PiT2). If not properly regulated, phosphate imblanace could lead to mineral disorders as well as vascular calcification. In chronic kidney disease-mineral bone disorder, hyperphosphataemia has been consistently associated with extra-osseous calcification and cardiovascular disease. This review focuses on the physiological mechanisms involved in phosphate balance and cell signalling (i.e. osteoblasts and vascular smooth muscle cells) as well as pathological consequences of hyperphosphataemia. Finally, conventional as well as new and experimental therapeutics in the treatment of hyperphosphataemia are explored.