The acute phase of hepatitis C (HCV) infection is typically defined as the initial 6 months following exposure to the virus; however, in some individuals, the acute phase of the infection can last much longer (Orland et al. Hepatology 33:321-27, 2001). Although some patients have symptoms of acute hepatitis, most infected individuals are entirely asymptomatic. As a result, many patients are unaware of the infection until it progresses to chronic infection, and may not develop symptoms until decades later with the onset of decompensated cirrhosis or hepatocellular carcinoma (HCC). A substantial proportion (20-40%) of infected patients clear the virus during the acute phase. Interferon-based treatment is also much more likely to be successful in the acute phase of infection but is relatively poorly tolerated. Therefore, recognition of acute HCV infection is critical to prioritize those patients who do not spontaneously clear the infection for immediate therapy. However, the promise of highly effective well-tolerated all-oral therapies in development may alter the management approach. This review will focus on the epidemiology, natural history, diagnosis, and treatment of acute HCV infection.