Studies on new direct-acting antivirals (DAAs) for hepatitis C virus infection were a focus of the 2011 Conference on Retroviruses and Opportunistic Infections. Although the majority of the data were from HIV-uninfected patients, much-needed work has begun to characterize DAA and antiretroviral drug interactions and to evaluate performance of DAAs for HIV/HCV-coinfected patients. There was continued emphasis on pathogenesis, management, and prevention of the long-term complications of HIV disease and its therapies, including cardiovascular disease, lipodystrophy, renal disease, and alterations in bone metabolism. Malignancies, particularly non-AIDS-defining cancers, have emerged as a leading complication and cause of death in HIV infection that may not be fully mitigated by immune reconstitution with antiretroviral therapy. This year's conference also highlighted important data on the optimal timing of antiretroviral therapy in tuberculosis coinfection, as well as the treatment and prevention of common coinfections including cryptococcal meningitis and influenza.