The aim is to review data on the epidemiology of fibroblast growth factor 23 (FGF23) and adverse clinical outcomes in chronic kidney disease (CKD) and introduce recent insights into the pathophysiology behind the observed relationships. End-stage renal disease and cardiovascular disease are frequent events in patients with CKD, in whom cardiovascular disease is the leading cause of death. Elevated levels of FGF23, a phosphate and vitamin D-regulating hormone, have been associated with risks of end-stage renal disease, cardiovascular disease and mortality. FGF23 excess has also been linked with left-ventricular hypertrophy, and innovative translational experiments have recently established direct end-organ toxicity of FGF23, which induced left-ventricular hypertrophy in animals. FGF23 is emerging as a novel risk factor in CKD. Future studies should determine whether interventions that lower FGF23 levels improve clinical outcomes in CKD.