Fibroblast growth factor (FGF) 23 is a bone-derived phosphotropic hormone that regulates phosphate and vitamin D metabolism. FGF23 mainly affects kidney function via the FGF receptor (FGFR)/α-Klotho complex. The physiological roles of FGF23 and α-Klotho in the regulation of mineral homeostasis have been well established. In addition, recent studies have reported that FGF23 has various effects on many other tissues, sometimes in an α-Klotho-independent manner, especially under pathological conditions. However, how FGF23 works in these tissues without α-Klotho is not entirely clear. Here we review the recent reports concerning the actions of FGF23 on various tissues and discuss the remaining questions about FGF23.