BACKGROUND AND AIMS: Progressive familial intrahepatic cholestasis (PFIC) is a collective term for a heterogenous group of rare, inherited cholestasis syndromes. The number of genes underlying the clinical PFIC phenotype is still increasing. While progressive liver disease and its sequelae such as portal hypertension, pruritus and hepatocellular carcinoma determine transplant-free survival, extrahepatic manifestations may cause relevant morbidity. METHODS: We performed a literature search for extrahepatic manifestations of PFIC associated with pathogenic gene variants in ATP8B1, ABCB11, ABCB4, TJP2, NR1H4 and MYO5B. To illustrate the extrahepatic symptoms described in the literature, PFIC cases from our centres were revisited. RESULTS: Extrahepatic symptoms are common in PFIC subtypes, where the affected gene is expressed at high levels in other tissues. While most liver-associated complications resolve after successful orthotopic liver transplantation (OLT), some extrahepatic symptoms show no response or even worsen after OLT. CONCLUSION: The spectrum of extrahepatic manifestations in PFIC highlights essential, non-redundant roles of the affected genes in other organs. Extrahepatic features contribute towards low health-related quality of life (HRQOL) and morbidity in PFIC. While OLT is often the only remaining, curative treatment, potential extrahepatic manifestations need to be carefully monitored and addressed.