Hepatitis C infection is characterised by three key features, which are the consequence of a complex interaction between genetic determinants of immune and other host factors and viral characteristics: 1. A high rate of viral persistence after acute infection resulting from a combination of weak T cell responsiveness and specific viral mechanisms of immune escape. 2. Marked interindividual variability in end-organ damage (fibrosis and cirrhosis), probably due to host genetic polymorphisms in genes governing the immune response and fibrosis pathways in addition to viral pathogenicity factors. 3. Significant resistance to antiviral therapies. Viral mechanisms of antiviral resistance parallel those of viral persistence, and include the intriguing possibility that hepatitis C may infect immunologically privileged sites such as the central nervous system.