Patients with chronic kidney disease (CKD) are at an increased risk of adverse cardiorenal outcomes, such as progressive kidney function loss, cardiovascular disease, and premature death. The hormone fibroblast growth factor 23 (FGF23) has come into view as a potential contributor to this cardiorenal risk in CKD. FGF23 is a regulator of phosphate balance in the human body. For unknown reasons, blood levels of FGF23 rise exponentially as kidney function declines. Higher FGF23 levels are subsequently associated with further deterioration of kidney function, heart failure, mortality, and other adverse health outcomes. This thesis explores novel determinants of FGF23 levels, as well as new connections between FGF23 and adverse cardiorenal outcomes. We show that iron deficiency and elevated erythropoietin (EPO) levels are associated with higher FGF23 levels in the general population, and that higher FGF23 levels in this population are associated with new-onset kidney disease and mortality. We also show that FGF23 plays a role in the association between iron deficiency and mortality in kidney transplant recipients. In a mouse model of kidney fibrosis, we found an interaction between FGF23 and medication commonly prescribed to CKD patients (RAAS blockade). We investigate the blood pressure curve measured from a finger as marker for cardiovascular risk. Lastly, we show that the glucose-lowering drug dapagliflozin increases blood phosphate and FGF23 levels, independent of effects on kidney function. Future intervention studies should establish whether the associations between FGF23 and adverse outcomes represent causal relationships, and whether interventions to lower FGF23 may improve these outcomes.