1. The natural history of hepatitis C after liver transplantation is variable. Several factors, including those related to the virus, the host, the environment and the donor, are probably implicated in the outcome. 2. The immune status per se likely represents the main significant variable in influencing disease severity in hepatitis C virus-infected patients. Findings that support this statement include the higher aggressivity of hepatitis C in immunocompromised liver transplant recipients as compared with that observed in immunocompetent patients, both before and after the development of compensated cirrhosis, and the significant association described between the degree of immunosuppression and disease severity. 3. Similar to that observed in the immunocompetent population, the age at the time of infection (age of the donor) strongly affects posttransplantation hepatitis C virus-related disease progression. 4. Hepatitis C-related disease progression is faster in patients who underwent transplantation in recent years as compared with those who underwent transplantation in earlier cohorts. The increasing age of the donor and the use of stronger immunosuppression may, in part, explain the worse outcomes seen in recent years. 5. Additional host-related variables predictive of outcome include the immunogenetic background, the timing of recurrence, and the early histologic findings.