Over the past decade, new roles for bile acids in paracrine and endocrine regulation of cholesterol homeostasis, lipid and carbohydrate metabolism and immunomodulatory functions have been discovered. Most of the early discoveries focused on the genomic actions of bile acids through the activation of families of nuclear receptors, such as the farnesoid X receptor and vitamin D receptors, until a new chapter in the bile acid receptor discovery unfolded in the form of TGR5; a novel G-protein-coupled receptor mediating several non-genomic functional responses induced by binding of bile acids. The key involvement of TGR5 in mediating energy homeostasis and glucose homeostasis made it an attractive target for the potential treatment of metabolic disorders.