Purpose of Review <p>Current prognostic scores and traditional biomarkers have notable limitations in predicting primary sclerosing cholangitis (PSC) disease course and the risk of PSC-related cholangiocarcinoma. This review will summarize the utility of these conventional methods and highlight recent advances in biomarker research for PSC and PSC-related cholangiocarcinoma.</p> Recent Findings <p>Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic, progressive fibroinflammatory damage to the bile ducts. Prognostication and monitoring of PSC pose significant challenges due to the rarity of the disease and the heterogeneity of its clinical phenotypes. Current noninvasive biomarkers of PSC are relatively nonspecific, leaving clinicians and researchers to primarily rely on prediction models. Recent studies have increasingly focused on identifying unique biomarkers specific to key aspects of PSC pathophysiology, including fibrosis, cholestasis, and immune activity.</p> Summary <p> This review emphasizes the growing number of novel noninvasive markers that hold promise in assessing PSC. Despite significant progress in the field, research has yet to identify a single noninvasive method that clearly outperforms traditional approaches. Ongoing research is crucial for establishing biomarkers that can be used for diagnosis, prognostication, and evaluation of therapeutic interventions. </p>