The HIV/AIDS pandemic has existed for >25 years. Extensive work globally has provided avenues to combat viral infection, but the disease continues to rage on in the human population and infected 4 million people in 2006 alone. In this review, we provide a brief history of HIV/AIDS, followed by analysis of one therapeutic target of HIV-1: its reverse transcriptase (RT). We discuss the biochemical characterization of RT in order to place emphasis on possible avenues of inhibition, which now includes both nucleoside and non-nucleoside modalities. Therapies against RT remain a cornerstone of anti-HIV treatment, but the virus eventually resists inhibition through the selection of drug-resistant RT mutations. Current inhibitors and associated resistance are discussed, with the hopes that new therapeutics can be developed against RT.--Basavapathruni, A., Anderson, K. S. Reverse transcription of the HIV-1 pandemic.