Highly active antiretroviral therapy with reverse transcriptase inhibitors(RTIs) and protease inhibitors(PIs) has achieved high-level suppression of viral load in HIV-1-infected patients. However, drug-resistant HIV-1 mutants often emerge, resulting in treatment failure. Various research attempts have been made to overcome the drug-resistance. At present, more than 200 amino acid mutations that confer resistance to anti-HIV-1 compounds have been reported. Furthermore, molecular mechanisms of the resistance induced by some RTIs and PIs have been well understood. Novel inhibitors effective against the resistant mutants have recently been discovered and are under clinical trials.