Chronic HCV infection is a non-traditional (but modifiable) risk factor for chronic kidney disease and has been implicated in glomerular injury and nephrosclerotic disease. Three HCV direct-acting antiviral regimens are available for patients with severe kidney impairment: ombitasvir, paritaprevir with the pharmacokinetic enhancer ritonavir, and dasabuvir; glecaprevir plus pibrentasvir; and elbasvir plus grazoprevir. In patients with severe kidney impairment, sofosbuvir-free regimens are preferred because sofosbuvir accumulation has been associated with a progressive worsening of renal function. In this Review, we provide our expert opinion on the current HCV treatment paradigm and highlight the remaining issues that need to be overcome to improve the treatment of HCV in this population.