Infection with hepatitis C virus (HCV) is the major cause of chronic liver disease that occurs after renal transplantation. Such infection is often acquired during dialysis while patients wait to undergo renal transplantation. Renal transplantation is considered the best treatment option for patients with HCV infection and end-stage renal disease, although acceptance of a kidney graft by the host immune system and patient survival are lower compared to patients who test negative for HCV. The approval of interferon-free therapies could substantially change the natural history of HCV infection after renal transplantation. This Review discusses the interplay between renal transplantation, HCV infection, and liver disease. We emphasize the development of novel therapeutic strategies, including use of the newly identified direct-acting antiviral agents for treating hepatitis C among infected patients. We next analyse the most common clinical complications subsequent to HCV infection and the impact on graft and patient survival. Finally, we evaluate the consequences of kidney transplantation from HCV-positive donors.