The article reviews the common molecular events and mechanisms underlying alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). Both diseases share similar evolutionary forms and are characterized by excessive fat accumulation in the liver, leading to liver fibrosis. The review highlights the gut microbiome's role in modulating lipid metabolism and inflammation, which is crucial in both AFLD and NAFLD. Key molecular events include lipid metabolism alterations, redox imbalance, and the role of adipokines. Cellular senescence, a stress-responsive program, also plays a significant role in the pathogenesis of both diseases. The article discusses the pathogenetic mechanisms of AFLD, such as ethanol oxidative metabolism and its impact on intracellular signaling pathways, as well as the inflammatory responses involved in NAFLD. High-fat diet and type 2 diabetes mellitus (T2DM) are identified as major risk factors for NAFLD. Therapeutic approaches for AFLD and NAFLD are explored, including nutritional support, silymarin, and targeting specific signaling pathways. The gut microbiome is highlighted as a key regulator of host physiology, with short-chain fatty acids (SCFAs) playing a protective role in NAFLD. The article also examines the role of cytokeratins and sirtuins in the pathogenesis of both diseases, suggesting potential therapeutic targets. Finally, the article discusses future directions, including the potential of n-3 polyunsaturated fatty acids (PUFAs) and the cGAS-STING pathway as therapeutic targets.The article reviews the common molecular events and mechanisms underlying alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). Both diseases share similar evolutionary forms and are characterized by excessive fat accumulation in the liver, leading to liver fibrosis. The review highlights the gut microbiome's role in modulating lipid metabolism and inflammation, which is crucial in both AFLD and NAFLD. Key molecular events include lipid metabolism alterations, redox imbalance, and the role of adipokines. Cellular senescence, a stress-responsive program, also plays a significant role in the pathogenesis of both diseases. The article discusses the pathogenetic mechanisms of AFLD, such as ethanol oxidative metabolism and its impact on intracellular signaling pathways, as well as the inflammatory responses involved in NAFLD. High-fat diet and type 2 diabetes mellitus (T2DM) are identified as major risk factors for NAFLD. Therapeutic approaches for AFLD and NAFLD are explored, including nutritional support, silymarin, and targeting specific signaling pathways. The gut microbiome is highlighted as a key regulator of host physiology, with short-chain fatty acids (SCFAs) playing a protective role in NAFLD. The article also examines the role of cytokeratins and sirtuins in the pathogenesis of both diseases, suggesting potential therapeutic targets. Finally, the article discusses future directions, including the potential of n-3 polyunsaturated fatty acids (PUFAs) and the cGAS-STING pathway as therapeutic targets.