The prevalence of alcohol use disorder has been steadily rising across the world in recent years, and exacerbating the burden of alcoholic liver disease (ALD) caused by chronic alcohol consumption has become one of the most important global health issues. ALD comprises a wide spectrum of liver injury including simple steatosis, steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. ALD is caused by the persistent intake of alcohol, and yet the detailed mechanisms of ALD progression remain vague. The development of ALD proceeds through complex signaling pathways in the liver. Chronic alcohol consumption not only elicits the various responses of innate immune cells in the liver, but also contributes to the metabolic dysfunctions of hepatocytes, such as the production of reactive oxygen species, the abnormal lipogenesis by endoplasmic reticulum stress or mitochondrial dysfunction, or the secretion of inflammatory cytokines. One of the key mechanisms underlying the development of alcoholic fatty liver is the enhancement of cannabinoid receptor 1 (CB1R)-mediated de novo lipogenesis in hepatocytes via the metabolic loop pathway. Chronic ethanol consumption induces hepatic CB1R-mediated alcoholic steatosis through DAGLβ-derived 2-AG production in hepatic stellate cells (HSCs). Recently, our group reported that alcoholic steatosis is promoted by metabotropic glutamate receptor 5 (mGluR5)-mediated endocannabinoid production in HSCs. These findings suggest a bidirectional paracrine loop between hepatocytes and HSCs, where both hepatocytes and HSCs can regulate each other by either producing a neurotransmitter or expressing its receptors. On the aspect of alcoholic steatohepatitis, we focused on the pro-inflammatory role of Kupffer cells (KCs). We hypothesized that glutamate is accumulated around central veins of hepatocytes after the chronic ethanol consumption and glutamate accumulation is regulated with the specific signaling pathway in the ethanol-fed mice. Ethanol binge drinking consecutively triggers glutamate release prompting mGluR5 activation of KCs to induce alcohol-induced inflammatory hepatic injury. The glutamate signaling also plays a pivotal role in liver fibrosis. Lately, we demonstrated that hepatocyte death increases extracellular levels of glutamate and activates mGluR5 of NK cells, which ultimately enhances the killing of activated HSCs by increasing cytotoxic cytokine production. In contrast, the glutamate uptake by activated HSCs in damaged areas leads to accelerated transdifferentiation of HSCs and suppresses mGluR5 activation of antifibrotic NK cells in advanced liver fibrosis. These results suggest that mGluR5 activation of NK cells could serve as a possible therapeutic target to intervene liver fibrosis. In summary, we proposed the “bidirectional signaling” that utilizes neurotransmitters, endocannabinoids, and their respective receptors to operate at a metabolic synapse among various hepatic cells. This novel concept could be a new mechanism for the development of ALD, proposing the possibility of its application as a novel pharmacological target, or plasma glutamate as a useful diagnostic marker for ALD.