Several new antiretroviral drugs have recently been licensed for use in HIV-1-infected patients. These include drugs in two new classes: an integrase inhibitor (raltegravir) and a CCR5 co-receptor antagonist (maraviroc). In addition, two new protease inhibitors, atazanavir and darunavir, which have activity against viruses resistant to other protease inhibitors, have come into clinical use. Finally etravirine, a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) is being increasingly used in patients whose virus is resistant to the earlier NNRTIs. These clinical advances have required the development of novel assays and interpretation systems for detection of resistance to allow the laboratory monitoring of patients receiving these new therapies.