Dysregulation of the key genetic, immunologic, and microbiome compounds of the gut-liver axis is the basis for inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC). This creates opportunities to accelerate therapies that have been traditionally developed for IBD to be used in PSC to the benefit of both diseases. Shared genetic susceptibility loci has yielded important clues into the pathogenesis of PSC-IBD. Understanding of the critical links between PSC and IBD are essential in designing clinical care pathways for these complex patients. Copyright © 2016 Elsevier Inc. All rights reserved.