Over the last decade, treatment options for chronic hepatitis B and hepatitis C infection have markedly evolved. Several Food and Drug Administration-approved drugs are now available for the treatment of chronic hepatitis B, including immunomodulators (standard and pegylated interferon alpha), nucleoside analogues (lamivudine, entecavir and telbivudine) and nucleotide analogues (adefovir dipivoxil and tenofovir). For hepatitis C, the FDA-approved therapies include peginterferon-α, ribavirin, boceprevir, telaprevir, simeprevir and sofosbuvir with expected approval of more agents in the foreseeable future. Some of these antiviral medications have been reported to have nephrotoxic effects, particularly with long-standing therapy, although the exact mechanism has not been fully elucidated. Secondary forms of glomerulonephritis that can be associated with hepatitis B and hepatitis C viral infection can further complicate the evaluation of renal failure in this population. Knowledge of the different antiviral medications and their potential nephrotoxic effects is crucial, since early identification and substitution to a different agent with withdrawal of the offending medication, may result in recovery or stabilization of renal function. Close monitoring of renal function while taking new antiviral medications is recommended, as some of the nephrotoxic effects may only appear after long-term use.