Inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), is associated with several hepatobiliary manifestations, most importantly primary sclerosing cholangitis (PSC). The association between these entities is bidirectional, though not necessarily causal, making the underlying pathogenesis challenging to decipher. While not yet fully elucidated, current evidence suggests that genetic and immunological factors play key roles in the coexistence of IBD and PSC. In this review, we aim to provide a comprehensive analysis from a clinical perspective, evaluating the association between PSC, PSC-associated cholangiocarcinoma, orthotopic liver transplantation for PSC, IBD, colitis-associated neoplasia and restorative proctocolectomy with ileal pouch-anal anastomosis for UC. Despite efforts of data collection through population-based registries, much of the existing evidence is based on small cohorts, often with low event rates and limited follow-up durations. This makes it challenging to draw definitive conclusions. Acknowledging the variability and heterogeneity of prior studies, we aim to offer valuable insight for gastroenterologists and hepatologists managing this unique and often challenging scenario, which some authors consider a new entity: PSC-IBD. Longitudinal studies with extended follow-up periods are needed to better understand the disease course of PSC and UC, including the impact of medical therapy, the development, surveillance and management of neoplasia, and the outcomes of surgery for both bowel and liver diseases.