The goal of treatment for acute hepatitis C patients is to eradicate the virus in the early phase of infection, thus preventing progression to chronicity. Early interferon (IFN) monotherapy has been shown to significantly reduce this risk, and therefore it has been recommended by international guidelines. To date, there is no standard treatment for the acute form of hepatitis C because available studies refer to small patient series receiving a variety of treatment regimens administered at varying time-points after onset of acute infection. Nevertheless, on the basis of published data, pegylated IFN monotherapy seems to offer the best therapeutic option because it is as effective as standard IFN monotherapy, and more convenient for the patient. Delaying treatment for 3 months after disease onset does not appear to reduce treatment efficacy and allows the identification of subjects with spontaneous resolution. It remains to be defined if an immediate treatment is more effective in patients with asymptomatic disease or those with genotype 1b. The optimal duration of Peg-IFN monotherapy should be 6 months. The efficacy of a 3-month course is under evaluation, especially for patients with clearance of HCV viremia within the first 4 weeks of therapy. There is no evidence that Peg-IFN/ribavirin combination therapy is more effective than Peg- IFN monotherapy, thus combination therapy might represent an alternative for patients who do not respond to IFN monotherapy or for HIV/HCV co-infected patients. Ongoing randomized controlled clinical trials should focus on unresolved questions and definitely establish the optimal treatment for acute hepatitis C.