Background: Cholangiocarcinoma (CCA) is the second most common primary liver cancer, being characterized by its late diagnosis and fatal outcome. Recent epidemiological reports indicate an increasing worldwide incidence of intrahepatic CCA but a decreasing incidence of extrahepatic CCA. Methods: In this review, we present an overview of the incidence and epidemiology of CCA and possible strategies for screening and surveillance. Results: Efficient strategies for the screening and surveillance of CCA have not been established so far. The vast majority of CCA occur sporadically without any apparent cause; however, several risk factors such as liver flukes, chronic biliary and liver diseases, and lifestyle-related aspects causing chronic inflammation and cholestasis in the liver have been linked to the development of CCA. These risk factors likely contribute to the increased incidence observed in some countries and also explain the wide geographical differences in the incidence of CCA. Conclusion: Several risk factors for CCA have been identified. Given the dismal prognosis of advanced CCA, regular surveillance examinations with a combination of ultrasonography and laboratory tests appear to be useful in patients at risk and need to be explored in prospective trials.