Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infected individuals have a higher risk of advanced liver fibrosis compared to those that are HCV mono-infected. Treatment of HCV offers the possibility of virus eradication, thus every person with detectable HCV viral load is a candidate for treatment. Treatment is recommended for all HCV/HIV co-infected patients with: 1) repeatedly elevated aminotransferase levels; 2) F2 stage of liver fibrosis or higher regardless of alanine aminotransferase level; and 3) more than 200 CD4+ T-lymphocytes per microL of blood. Treatment is not recommended for patients that are active injection drug users, consume large amounts of alcohol, or have or had a severe psychiatric disorder. Liver biopsy is generally recommended, however, because of faster progression to liver fibrosis in HIV and HCV co-infected patients, if the patient declines liver biopsy it should not exclude him from treatment. Treatment with a combination of pegylated interferon and weight-based ribavirin (1000 mg/day if <75 kg and 1200 mg/day if >75 kg) is recommended. Pegylated interferon is used as 180 microg for alfa-2a form and 1.5 mg/kg for alfa-2b form once weekly subcutaneously. HCV RNA should be measured after 4 weeks of treatment, and later as needed, in weeks 12, 24, 48 or 72. For evaluation of a sustained viral response, HCV RNA should be measured 24 weeks after the end of treatment. In patients with rapid viral response (undetectable levels of HCV RNA after 4 weeks of treatment), treatment duration is 24 weeks (genotypes 2 and 3) or 48 weeks (genotypes 1 and 4). In patients without rapid viral response but with an adequate response after 12 and 24 weeks, we generally recommend treatment for 48 weeks, however, 72 weeks of treatment can be considered for genotypes 1 and 4. Treatment discontinuation is recommended in patients with <2 log viral load decline after 12 weeks or with a detectable viral load after 24 weeks of treatment. If concurrent treatment of HCV and HIV is necessary, treatment with zidovudine and didanosine should be avoided and caution is needed with the administration of potentially hepatotoxic antiretroviral drugs such as nevirapine and ritonavir.