Editors 2013 The Reverse Transcriptase (RT) of Human Immunodefi ciency Virus Type 1 (HIV-1) arguably ranks among one of the most extensively studied retroviral enzymes. Heterologous expression and purifi cation of HIV-1 RT in the early 1980s, approval of the fi rst nucleoside analogue RT inhibitor (NRTI) in 1987, discovery of resistance to RT inhibitors, and approval of the first nonnucleoside analogue RT inhibitor (NNRTI) in 1996 and the various crystal structures of RT with or without bound substrate(s) and/or inhibitors represent only a few of the important milestones that describe a bench-to-bedside success in the continuing effort to combat HIV-1 infection and its consequences.