Combination antiretroviral therapy reduces overall and liver-specific morbidity and mortality in coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) and represents the most beneficial pharmaceutical treatment intervention for most coinfected patients. Antiviral therapy for HCV infection is potentially organ- and life-saving but, in general, should be reserved for patients who achieve suppression of HIV RNA and immune restoration from combination antiretroviral therapy or for patients with nadir CD4+ T lymphocyte levels of >350 cells/microL. Safe and virologically active treatment of coinfection with HIV and hepatitis B virus can be concurrently achieved by the use of combination antiretroviral therapy regimens containing lamivudine and/or tenofovir.