Fibroblast growth factor 21 (FGF21) is a circulating protein composed of 181 amino acids that belongs to the FGF superfamily and performs important metabolic functions. The expression of b-Klotho is highly correlated with metabolically active tissues, where it interacts with specific FGF receptors to exert its effect. Adipocytes respond positively to FGF21 because it increases glucose absorption by inducing glucose transporter-1. The effect is cumulative and insulin-independent. This protein protects b-cell function and survival, decreases glucagon secretion, and enhances insulin sensitivity by lowering hepatic glucose synthesis. Several animal models have demonstrated that FGF21 can enhance lipid profile. FGF21 causes weight loss in diabetic nonhuman primates and increases energy expenditure in rats. In rodents, it has a beneficial effect on hepatic steatosis and lowers tissue lipid content. It appears that FGF21 mediates some of the metabolic adaptations to fasting. These include the increased rate of ketogenesis and fatty acid oxidation. Insulin-resistant states, like reduced glucose tolerance and type 2 diabetes, are associated with increased serum FGF21 concentrations in humans. Hepatic insulin resistance index, fasting blood glucose, hemoglobin A1c, and postprandial glucose all correlate with FGF21 levels. Nephropathy and carotid atheromatosis are two of the long-term consequences of diabetes that have been linked to elevated FGF21 levels. Patients with diabetes whose FGF21 levels dropped after beginning treatment with insulin or oral medications. High levels of FGF21 in the blood have also been linked to being overweight. FGF21 levels are predominantly associated to numerous components of the metabolic syndrome in adults, whereas in children it is correlated with body mass index and leptin levels. Patients with ischemic heart disease have been reported to have higher serum FGF21 levels. The levels of FGF21 in patients with renal illness rose steadily alongside the decline in renal function. Dialysis patients had elevated levels of circulating FGF21, which has been linked to insulin resistance and inflammation. In conclusion, FGF21 is a newly discovered hormone that has been shown to reduce blood sugar, fat in the blood, and body temperature. Insulin resistance could be treated by boosting its actions, either directly or indirectly.