Elsulfavirine (Elpida®) is a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) being developed by Viriom for the treatment and prevention of human immunodeficiency virus (HIV) infections. It is the prodrug of the active compound VM-1500A, a small molecule selective NNRTI, which prevents HIV replication. In June 2017, elsulfavirine received its first global approval in Russia for the treatment of HIV-1 infections in combination with other antiretroviral medicines. Other formulations of this drug are also being evaluated in preclinical and phase II studies for the treatment of HIV infections and/or pre-exposure and post-exposure prophylaxis. This article summarizes the milestones in the development of elsulfavirine leading to this first approval in HIV-1 treatment.