OBJECTIVE This review focuses on the use of tipranavir/ritonavir, darunavir/ritonavir and etravirine for the treatment of HIV infection that has become resistant to protease inhibitors and/or nonnucleoside reverse transcriptase inhibitors. RESULTS Tipranavir/ritonavir and darunavir/ritonavir are boosted protease inhibitors highly active against HIV that has developed mutations that confer resistance to other protease inhibitors. For both drugs, there are scores to predict activity based on a combination of mutations. Best results are obtained when each drug is combined with one and preferably two other completely active antiretrovirals. The interaction profile and toxicity profile is better for darunavir/ritonavir, which in addition has shown positive outcomes in clinical trials of patients with early failure.Etravirine is a nonnucleoside reverse transcriptase inhibitor highly active against HIV that has developed mutations that confer resistance to nevirapine or efavirenz. Clinical trials results suggest that etravirine should be used with other active antiretrovirals. Best results for etravirine have been obtained in combination with darunavir/ritonavir in patients with extensive protease inhibitor and nonnucleoside reverse transcriptase inhibitor resistance. The role of etravirine for the treatment of early failure of efavirenz-based or nevirapine-based regimens remains to be elucidated. Resistance to etravirine requires the accumulation of multiple reverse transcriptase mutations different from K103N, which has no impact on activity. CONCLUSIONS Tipranavir/ritonavir, darunavir/ritonavir and etravirine are very important additions to the therapeutic armamentarium against HIV that has become resistant to protease inhibitors and nonnucleoside reverse transcriptase inhibitors.