Treatment for chronic viral hepatitis C has advanced dramatically to current standard of care all-oral direct-acting antiviral regimens with relatively short treatment duration and high efficacy. Patients with comorbid end-stage renal disease have constituted a “special patient population” with data and treatment options lagging behind that of the broader population of patients with chronic hepatitis C until recently. Herein we review the current evidence base for direct-acting antiviral therapy in this population. We provide a suggested algorithm for the evaluation of such patients for therapy. We highlight special considerations in regards to the choice of regimen, duration, and timing in regards to potential kidney transplantation.