Background: Cholangiocarcinoma (CCA) is an epithelial tumor with features of cholangiocyte differentiation. Most patients suffer from a nonresectable disease since presentation and the exitus occurs within 12 months from diagnosis. Biliary epithelial carcinogenesis is a multistep process that involves the transition from hyperplasia to dysplasia to carcinoma. The clinical approach should be multidisciplinary, and the diagnosis should be considered when there is a histological finding of adenocarcinoma without any other evidences of an extrahepatic primitive neoplasia. Surgical resection with histologically negative margins is the only curative treatment. Nevertheless for unresectable patients, there are several other approaches: systemic chemotherapy is the widely used treatment, but a large proportion of patients could be suitable for liver-directed therapies. These options include transarterial chemoembolization (TACE), radioembolization (TARE), hepatic arterial infusion (HAI), percutaneous ablation, and external beam radiation therapy (EBRT). Conclusion: Intrahepatic cholangiocarcinoma is a relatively rare disease with a poor prognosis. Diagnosis is based on imaging, but pathological anatomy plays an important role. Surgery is still the gold standard treatment; nevertheless, unresectable patients could be treated in a multimodality strategy with a significant improvement in terms of survival.