Despite major advances in therapy of hepatitis C over the past decade, nearly half of the patients treated with the currently available regimens do not clear the virus. Therefore, there is a large unmet need for more effective therapy for patients who have failed pegylated interferon plus ribavirin therapy. We describe a case of a HCV genotype 1b patient who had failed previous combination therapies of interferon plus ribavirin and pegylated interferon plus ribavirin and was subsequently successfully treated with a novel triple drug combination consisting of interferon-γ plus interferon alfacon plus ribavirin with the outcome of a sustained virologic response. This triple drug therapy combination could be an option for patients who have failed therapies with currently available pegylated interferons plus ribavirin. Prospective randomized studies are required to evaluate the effectiveness and tolerability of this regimen in this patient population.