Abstract The gut is open to the outer environment, harbours the microbiome containing several fold more genetic material than the human genome and produces a myriad of metabolites as well as hormones/peptides. The liver is at the nexus between this vast source of nutrients, toxins and hormones and the remaining human body. Not surprisingly, this liver-gut-axis has hence, been demonstrated in experimental models and in-vitro systems to contribute to the pathogenesis of most liver diseases such as alcoholic and non-alcoholic fatty liver disease (NAFLD), -steatohepatitis (NASH), cholestatic liver diseases, hepatocellular carcinoma, acute-on-chronic liver failure, progression to fibrosis/cirrhosis and complications of cirrhosis. Therapeutic approaches can be grouped into modulation of the microbiota, the bile acid pool and/or its signaling, gut-lumen adsorptive strategies, bariatric procedures, incretins and miscellaneous (e.g.prokinetics). However, in order to proof these concepts investigations in humans are key and thus, this article will highlight the most recent human studies and clinical trials targeting the liver-gut-axis. A list of ongoing (not yet published) trials is presented in table 1. Moreover, we will take the liberty to encourage clinical trials on concepts that are so far not yet established.