HIV accelerates progression of hepatitis C virus (HCV)-related liver disease. There are conflicting data on the effect of HCV on the risk of HIV progression and CD4 response to highly active antiretroviral therapy (HAART). Long-term prospective cohort studies are clearly required to resolve these issues. The optimal management of the co-infected patient is also unclear. For the co-infected patient, the optimal HAART regimen for best immune CD4 recovery and least adverse reactions remains unclear. Unfortunately, current HCV treatment is associated with significant side effects and a considerable proportion of HIV co-infected patients are poor candidates for HCV treatment. Better and more effective treatment for HCV (preferably not based on interferon) is urgently required for this group of patients. Patients with good CD4 cell count and with HCV genotypes 2 and 3 are likely to have a reasonable response to treatment.