Aside from facilitating solubilisation and absorption of dietary lipids and lipid-soluble vitamins, amphipathic bile acids (BAs) also act as bioactive signalling molecules. A plethora of conjugated or un-conjugated primary and bacterially-modified secondary BA moieties have been identified, with significant divergence between species. These molecules are excreted into the external environment of the intestinal lumen, yet nuclear and membrane receptors that are sensitive to BAs are expressed internally in the liver, intestinal and neural tissues, amongst others. The diversity of BAs and receptors underpins the multitude of distinct bioactive functions attributed to BAs, but also hampers elucidation of the physiological mechanisms underpinning these actions. In this topical review, we have considered the potential of BAs as cross-barrier signalling molecules that contribute to interoceptive pathways informing the central nervous system of environmental changes in the gut lumen. Activation of BAs on FGF19 -secreting enterocytes, enteroendocrine cells coupled to sensory nerves or intestinal immune cells would facilitate indirect signalling, whereas direct activation of BA receptors in the brain are likely to occur primarily under pathophysiological conditions when concentrations of BAs are elevated. Abstract figure legend The figure illustrates the microbial modification of hepatic primary bile acids into secondary bile acids. In addition to facilitating lipid digestion and absorption, bile acids act as bioactive signalling molecules by binding to bile acid receptors expressed on enterocytes, neural afferent-coupled enteroendocrine cells and immune cells. This article is protected by copyright. All rights reserved.