The 44 crystal structures of NNRTIs complexed with HIV-1 reverse transcriptase (RT) have been analyzed in detail especially the orientation geometries and the distances between inhibitor molecules and surrounding amino acids. In general, various NNIs bind to the same region of the HIV-1 RT in the palm subdomain of p66, but subtle differences in individual interactions between RT and its inhibitors can be detected by comparison of all structures in this study.