Although acute hepatitis C virus (HCV) infection is a rare disease and typically not associated with severe clinical symptoms, it has become a disease of significant interest for clinical investigators, virologists, and immunologists alike. In the same way that acute hepatitis C provided a window of opportunity for understanding the clinical and virological aspects of HCV infection as the field was being established, it is now clear that it can provide a window into further understanding the early interaction of the virus with the host immune response. The acute phase of infection is usually considered to be the first 6 months; however, rather than defining acute HCV by the time that has passed after initial infection, it can also be defined as the biological state in which spontaneous clearance is still possible.