Given the advent of highly effective interferon (IFN)-free direct-acting antivirals (DAAs), this review aims to provide evidence to help determine whether doctors should prefer the "watch and wait" or "treatment for all" approach for chronic hepatitis C virus (HCV) infection. The novel treatment regimens usually consist of a 12 week course of both a NS5A inhibitor and a NS5B polymerase inhibitor, and result in excellent sustained virological response (SVR) rates of >90%. NS5A/NS5B inhibitor combinations are also highly effective for previously "difficult-to-treat" and/or "difficult-to-cure" HCV subgroups including patients with cirrhosis, HIV/HCV co-infection, or recurrent HCV infection after liver transplantation. An individualized treatment plan based on careful evaluation of the severity of the disease (need) versus the expected outcome (efficacy) while considering potentially severe side effects (safety) and the socioeconomic situation (costs) seems to be the most reasonable approach. Achieving SVR in patients with advanced cirrhosis represents a virological "cure" but does not universally prevent decompensation or completely abolish the risk of hepatocellular carcinoma (HCC) development. Thus, patients with advanced cirrhosis still need to be monitored after SVR for hepatic decompensation and must undergo regular HCC screening. Economic barriers likely represents a major hurdle for the universal use of the novel IFN-free DAA regimens. Local policies differ amongst health-care systems and reimbursement for DAA-based (ideally IFN-free) treatment regimens is often limited to certain HCV patient groups depending on individual need, expected efficacy, and available safety/efficacy data of the respective treatment regimen.