Progression from acute to chronic HCV infection occurs in 50% to 84% of cases. In light of the risk of developing chronic disease and the response rate to treatment once the disease is established, it is important to consider early treatment of acute HCV infection before it progresses to the chronic state. Several studies evaluated the efficacy of either alpha or beta IFN monotherapy in patients with acute hepatitis C, but nearly all trials are small and present great variability regarding timing, schedule, response definition and patient characteristics. To overcome these limits, IFN efficacy has been assessed by meta-analyses demonstrating that antiviral therapy during the acute phase of HCV significantly reduces evolution to chronic hepatitis. Accordingly, treatment of persons with acute hepatitis C is warranted. However, several issues remain to be addressed, such as the optimal regimen and timing. Recent data would indicate that induction with daily IFN is needed to optimize response and pegylated IFN monotherapy could be the best option. Combination therapy with ribavirin does not seem to increase the response rate but could be proposed as a second choice to patients non responding to IFN monotherapy. Delaying treatment by 2-3 months might allow the identification of cases who would spontaneously resolve without compromising efficacy. However, additional data are required to improve the selection of those patients at great risk of progressing to chronic disease, and also to establish the optimal treatment in terms of risk / benefit and cost-effectiveness ratio.