The frequency of hepatitis C virus (HCV) infection remains high in patients with chronic kidney disease (CKD) and plays a detrimental role in mortality in this population. According to the latest survey, the adjusted hazard ratio for HCV-positive versus HCV-negative patients on long-term dialysis was 1.12 (95% CI, 1.05 to 1.20) and 1.10 (95% CI, 0.98 to 1.22) for all-cause and cardiovascular mortality, respectively. An impairment on quality of life has also been documented in HCV-infected patients undergoing regular dialysis. Most clinicians have been so far reluctant to treat hepatitis C in patients with advanced CKD, due to concerns regarding low efficacy and safety of interferon-based regimens. The advent of all-oral, direct-acting antivirals (DAAs) has revolutionized treatment paradigms for HCV, including patients with other comorbidities such as CKD. Two combinations of DAAs have been recently approved for the treatment of HCV in advanced CKD: elbasvir/grazoprevir (evaluated in 1 randomized controlled trial) and ombitasvir/paritaprevir/ritonavir/dasabuvir with or without ribavirin (examined in some observational, single-arm studies). These antiviral combinations have provided high safety and efficacy (SVR12 rates >90%) in HCV-infected patients with stage 4-5 CKD. Sofosbuvir, a nucleotide analogue inhibitor of the HCV NS5B polymerase, is the cornerstone of most anti-HCV current regimens but is not currently recommended for patients with severe renal insufficiency (eGFR <30 mL/min per 1.73 m2). However, several small-sized studies have been published on the safety and efficacy of sofosbuvir-based regimens for patients with hepatitis C on maintenance dialysis; overall, the viral response was satisfactory (SVR12 rates ranging between 58% and 100%) with a few drug-related drop-outs. Studies are in progress to assess whether ribavirin-free antiviral combinations with novel DAAs are a viable option for patients with severe renal impairment and chronic HCV infection.