<p>Sclerosing cholangitis encompasses a group of conditions eventually leading to chronic cholestasis, and are characterized by inflammation, fibrosis, and segmental strictures of the intrahepatic and/or extrahepatic ducts. These can be either primary or secondary in origin. Primary sclerosing cholangitis (PSC) has no identifiable cause, while secondary sclerosing cholangitis (SSC) has various causes, producing similar chronic progressive changes in the biliary ducts. It is vital to differentiate between the two, as PSC is difficult to treat (with liver transplantation being the definitive treatment), while many causes of SSC are treatable, and even reversible. Therefore, it is imperative to exclude secondary causes of sclerosing cholangitis before establishing the diagnosis of PSC. While MRCP is the non-invasive imaging gold standard, ERCP, clinical correlation, and biopsy are frequently required to establish a definitive diagnosis. This review article presents a systematic approach to the imaging-based differential diagnoses of sclerosing cholangitis, integrating key clinical, laboratory, and radiological features.</p> Graphical Abstract <p></p>