As a result of shared routes of transmission, coinfection with hepatitis C virus (HCV) is common in human immunodeficiency virus (HIV)–infected patients. The prevalence of HIV/HCV coinfection is particularly high among persons who have used injection drugs; however, more recently, sexual transmission of HCV has been recognized among HIV-infected men who have sex with men (MSM). Over the past decade, the effectiveness of HIV treatment improved substantially, leading to a substantial reduction in HIV/AIDS-related deaths; in this context, liver disease due to HCV infection has emerged as major concern for co-infected patients. Over the same period, treatment of HCV remained stagnant, with pegylated interferon alfa (PegIFN) plus ribavirin (RBV; PegIFN/RBV) entrenched as the standard treatment for HCV infection for co-infected patients, who have the greatest risk for liver disease. However, the effectiveness of HCV treatment in this population has been disappointing because of low rates of treatment initiation and success. In 2011, novel HCV NS3/4A PIs (PIs), telaprevir and boceprevir, were approved for use in combination with PegIFN/RBV for the treatment of HCV genotype 1 infection; at the time of approval, important questions regarding the efficacy, safety, and potential for drug interactions with telaprevir and boceprevir had not been answered. More recently, data from drug-interaction studies and 2 small, phase II clinical trials indicate that these HCV treatment regimens may lead to higher rates of HCV eradication in HIV/HCV-coinfected patients, with manageable toxicity and pharmacologic interactions with antiretroviral drugs. As such, these HCV PI–based regimens have emerged as the standard for the treatment of HCV genotype 1 infection in carefully selected HIV-infected patients.