Highly active anti-retroviral therapy(HAART) using two or more reverse transcriptase inhibitors(RTIs) and protease inhibitors, has dramatically improves the quality of life and survival of patients infected with human immunodeficiency virus(HIV). RTIs are categorized by their mechanism of action, into two groups, nucleoside(N) and non-nucleoside(NN) RTIs. However, resistant HIV variants against NRTIs and/or NNRTIs including multi-drug resistant, emerge after the prolonged therapy. To suppress the replication of such resistant variants, numerous anti-HIV drugs have been developed. In this review, the mechanisms of action and characters of the major drugs in clinical or under preclinical are described.