Fetuins are blood proteins that are made in the liver and secreted into the bloodstream. They belong to a large group of binding proteins mediating the transport and availability of a wide variety of cargo substances in the bloodstream. Human fetuin is synonymous with α2-HS-glycoprotein (genetic symbol AHSG), α2-HS, A2HS, AHS, HSGA, and fetuin-A. Fetuin-A is regarded as a potent inhibitor of systemic calcification in gene knock-out mice. It has been demonstrated to play an important role in free fatty acid induced insulin resistance at liver. Fetuin-A is a predictor of adverse glycemic outcomes in pre-diabetes. It has been also been linked to increased occurrence of non-alcoholic fatty liver disease and cardiovascular events. It is a negative acute-phase reactant in sepsis and endotoxemia, promotes wound healing, and is neuroprotective in Alzheimer’s disease. Decreased fetuin-A is a predictor of increased disease activity in obstructive lung disease, Crohn’s disease, and ulcerative colitis.