The serum vitamin D binding protein (DBP), also known as GC-globulin, is a multifunctional protein known for its role in the transport of vitamin D metabolites. DBP also binds fatty acids and actin monomers, preventing their polymerization that could be detrimental in the circulatory system. DBP may have immune functions independent of its role as a transporter of vitamin D. Because of the abundance of DBP, many aspects of its basic biochemistry were quickly established. Other features of vitamin D action, particularly transcriptional mechanisms of regulation, received greater focus and early interest in DBP centred on its value as a tool for population genetics because of its intriguing genetic variations. Nonetheless, knowledge of DBP mechanisms in physiology was obtained, and functions beyond vitamin D ligand binding were identified. With the recent increased attention regarding the benefits of vitamin D (bone health and immunological regulation), there has been a resurgence of interest in DBP. Because DBP is the primary transporter of vitamin D, it has a role in maintaining the total levels of vitamin D for the organism and in regulating the amounts of free (unbound) vitamin D available for specific tissues and cell types to utilize. This review will describe the findings on the basic biochemistry and molecular biology of DBP, the studies that elucidated its biological functions and highlight these results in light of the current renewed interest in vitamin D and human health, as well as the debate over what constitutes sufficient levels of vitamin D. Copyright © 2012 John Wiley & Sons, Ltd.