Since its characterization in 1989, hepatitis C virus (HCV) chronic infection has been a leading cause of liver-related morbidity and mortality. In the year 2015, the World Health Organization estimated that 71 million people were infected with HCV. Furthermore, in 2016 approximately 400,000 individuals with HCV infection died due to complications of cirrhosis or hepatocellular carcinoma (HCC).1 This data offers insights of the magnitude of the problem. In the last decades, physicians treating liver conditions have witnessed an unequivocal historic breakthrough. The advent of direct-acting antiviral agents (DAAs), enabling highly effective interferon-free regimens, has fundamentally transformed the landscape. While tolerance or efficacy issues are part of the past, new challenges emerge when managing patients with sustained virologic response (SVR) after DAAs treatment. Relevant questions regarding how to evaluate the risk of HCC or how to non-invasively stage liver fibrosis after SVR have not been yet properly answered. In the present manuscript we seek to explore the Top 5 current dilemmas frequently faced in HCV clinics (Fig. 1).