Liver disease is a major global health problem leading to approximately two million deaths a year. This is the consequence of a number of aetiologies, including alcohol-related, metabolic-related, viral infection, cholestatic and immune disease, leading to fibrosis and, eventually, cirrhosis. No specific registered antifibrotic therapies exist to reverse liver injury, so current treatment aims at managing the underlying factors to mitigate the development of liver disease. There are bidirectional feedback loops between the liver and the rest of the gastrointestinal tract via the portal venous and biliary systems, which are mediated by microbial metabolites, specifically short-chain fatty acids (SCFAs) and secondary bile acids. The interaction between the liver and the gastrointestinal microbiome has the potential to provide a novel therapeutic modality to mitigate the progression of liver disease and its complications. This review will outline our understanding of hepatic fibrosis, liver disease, and its connection to the microbiome, which may identify potential therapeutic targets or strategies to mitigate liver disease.