Fetuin was first isolated from bovine serum in 1944. It is now most commonly known as either fetuin-A or alpha-2-HS-glycoprotein (AHSG), the protein product of Ahsg gene. A prominent feature of this protein is the functional diversity exerted in human physiology and pathophysiology. Fetuin-A plays a role in bone metabolism, metabolic disorders such as insulin resistance and diabetes mellitus (DM), and central nervous system (CNS) disorders such as ischemic stroke (IS) and neurodegenerative diseases. In addition, emerging evidence suggests involvement of fetuin-A in the cardiovascular system. However, there are many discordant findings on the associations between fetuin-A and vascular diseases. In other words, it is unknown whether fetuin-A is an exacerbating or a protective factor in the cardiovascular system. One reason for the seemingly inconsistent behavior is the dual functionality of fetuin-A in vascular diseases where it can act as an atherogenic factor or as a vascular calcification inhibitor. In addition, the existence of confounding factors such as DM and renal dysfunction can veil the primary association between fetuin-A and clinical parameters. Considering these issues, we discuss the role of fetuin-A for atherosclerosis and vascular calcification in this review.