Managing chronic hepatitis C in patients coinfected with the human immunodeficiency virus is a significant challenge. Treatment is influenced by a number of viral and host characteristics, including hepatitis C virus genotype, baseline viremia, and adherence to medication. Accelerated progression of liver disease, immunodeficiency, and hepatotoxicity of antiretroviral drugs are additional concerns in coinfected patients. According to the results of 5 randomized clinical trials, 27 %-55 % of coinfected patients who receive therapy with peginterferon alfa plus ribavirin attain sustained virologic response. These studies also confirm the importance of early virologic response as a predictor of treatment outcome and reveal the considerable proportion of patients who experience hematologic tolerability issues. Effective management strategies that encompass patient and viral factors are necessary to improve the long-term outlook for coinfected patients.