Liver cancer is a major global health problem whose incidence is on the rise. The improvement in the understanding of the pathogenesis, early detection, diagnosis, staging and treatment of liver cancer has been enormous. The landscape of molecular aberrations driving both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) have been unravelled. Several breakthroughs have occurred in the prevention, surveillance and treatment of HCC. Particularly, management of patients at advanced stages has changed dramatically during the last decade with the advent of effective systemic therapies such as sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab. iCCA has long been considered a difficult to treat disease with few therapeutic options. However, recent advances in our understanding of its molecular pathogenesis, as well as the development of adjuvant therapy (capecitabine) and new systemic treatments (gemcitabine and cisplatin) have paved the way for further innovations in the management of patients with iCCA. In this manuscript, we aimed to highlight the main milestones in the medical history of primary liver cancer and report the most recent developments described within this special issue.