Bile acids are mainly recognized for their role in dietary lipid absorption and cholesterol homeostasis. However, recent progress in bile acid research suggests that bile acids are important signaling molecules that play a role in glucose homeostasis. Among the various supporting evidence, several reports have demonstrated an improvement of the glycemic index of type 2 diabetic patients treated with diverse bile acid binding resins. Herein, we review the diverse interactions of bile acids with various signaling/response pathways, including calcium mobilization and protein kinase activation, membrane receptor-mediated responses, and nuclear receptor responses. Some of the effects of the bile acids are direct through the activation of specific receptors, i.e., TGR5, CAR, VDR, and FXR, while others imply modulation of the hormonal, growth factor and/or neuromediator responses, i.e., glucagon, EGF, and acetylcholine. We also discuss recent evidence implicating the interaction of bile acids with glucose homeostasis mechanisms, with the integration of our understanding of how the signaling mechanisms modulated by bile acid could regulate glucose metabolism.