The skeleton is able to secrete hormones and mediate endocrine functions. Particularly, the fibroblast growth factor 23 (FGF23) has received considerable attention for its unique phosphaturic properties, raising the bone to the status of an essential endocrine regulator. Excess in circulating levels of FGF23, not so surprisingly, then associated to mineral imbalance, in hereditary/acquired mineral and skeletal disorders. A key player, FGF23 excess precedes mineral and skeletal disturbances. However, unexpected effects have been described in the recent years. Various demonstrations have been made that FGF23 is directly regulated by non-mineral stress, including: inflammation, iron deficiency, and glycolysis. In turn, an emerging body of research shows association and causality between FGF23 and the cardiovascular system at large, from the iron metabolism to erythropoiesis, and to the cardiac muscle. This review summarizes canonical and novel effects of FGF23. FGF23 cleavage generates C-terminal peptides that also mediate biological functions. In aggregate, FGF23 measurements should be considered for larger application, as its excess can precede hypophosphatemia, explain hypophosphatemia or resistance to phosphate loading, and possibly predict cardiovascular progression in a wide range of uremic and non-uremic conditions.