Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. It is the second most common type of primary liver tumors with increasing incidence worldwide. CCA is deadly due to its ability to recur, metastasize, late diagnosis and drug-refractory nature. The etiopathogenesis of this disease remains still obscure. However, over the last period of time, an intense research shed new light on understanding the pathophysiology of CCA. Thus, novel perspectives for disease management and therapy have been opened.