Fibroblast growth factor can be measured in clinical practice using ELISA, with acceptable validity. Different from many metabolites and minerals, its value can differ by a thousand-fold between individuals, largely because of differences in kidney function and dietary habits. This wide range complicates the proper interpretation of the concentration of FGF23, both in terms of the appropriateness of a given value for a given estimated GFR, and in terms of estimating the magnitude of risk for clinical events, with which FGF23 is clearly associated. In this narrative review, the impact of kidney function, exposure to phosphate from diet, and novel emerging factors that influence FGF23 concentrations are discussed. These and yet to define determinants of FGF23 question the causality of the association of FGF23 with hard (cardiovascular) endpoints, as observed in several epidemiological studies.