Dolutegravir, an orally administered HIV-1 integrase strand transfer inhibitor (INSTI), is under development by ViiV Healthcare. Like other drugs belonging in the INSTI class of antiretroviral agents, dolutegravir binds to the integrase site of HIV-1 and blocks the strand transfer integration step, thereby preventing the replication of HIV-1. Dolutegravir is being developed as an unboosted once-daily therapy for use in combination with other antiretroviral agents for the treatment of both treatment-naïve and treatment-experienced patients with HIV-1 infection. Dolutegravir has been approved in the USA for the treatment of HIV-1 infection in combination with other antiretroviral agents and has been filed for approval in the EU and Canada. Phase III development is underway in North America, Europe, South Africa, South America, Australia and Taiwan. This article summarizes the milestones in the development of dolutegravir leading to this first approval for the treatment of HIV-1 infection in both therapy-naïve and -experienced patients.