Traditionally, bile acids (BA) have been viewed as detergent molecules involved in the intestinal digestion and absorption of lipids and hepatic maintenance of cholesterol homeostasis. During the last 15 years, however, it has become clear that BA are important regulatory molecules with systemic endocrine functions that signal changes in luminal nutrients and microbial activity during the fed-fast cycle. The regulatory actions of BA are primarily mediated by the nuclear receptor FXR (farnesoid X receptor), the G-protein coupled receptor TGR5 and cellular signaling pathways (AKT and ERK1/2). These proteins are highly expressed in the liver as well as enterocytes, endocrine cells and enteric neurons in the small intestine. Surprisingly, BA receptors are also present in several tissues outside the biliary tree including adipose tissue, pancreas, and immune cells. In mice, via interaction with these sensors and pathways, BA control the expression of genes and concentration of circulating hormones involved in the regulation of lipid and glucose metabolism, energy expenditure, intestinal integrity, motility, and immune homeostasis, gut microbial growth, and inflammation. In pigs, evidence from seminal studies indicates that BA signaling is implicated in the intestinal secretion of glucagon-like peptides, gut mucosal growth and protection, nutrition-related liver disease, and changes in host weight and metabolism resulting from variations in gut microbiota. It is important to note that BA differ in their ability to activate signaling pathways and that the composition of the BA pool varies remarkably among non-ruminant animals. In fact, all non-ruminant species of interest (e.g., pig, chicken, rabbit, horse) have unique BA signatures. In view of these differences and the emerging role of BA as regulatory molecules, the study of their involvement in signaling outside the enterohepatic circulation and in mediating reciprocal communication between the host and its microbiota will become a relevant and expanding field of research in animal nutrition and physiology.