Chronic liver disease is reaching epidemic proportions with the increasing prevalence of obesity, non-alcoholic liver disease, and alcohol overuse worldwide. Most patients with are not candidates for liver transplantation, even if they have end-stage liver disease. There is growing evidence of a gut microbial basis for many liver diseases, therefore, better diagnostic, prognostic, and therapeutic approaches based on knowledge of gut microbiota are needed. We review the questions that need to be answered to successfully translate knowledge our knowledge of the intestinal microbiome and the changes associated with liver disease into practice.