Islatravir is the first drug of a new class called nucleoside reverse transcriptase translocation inhibitors (NRTTIs). Its new mechanism of action and its long-acting properties have the potential to make it an important product in HIV treatment. After a period of pause in clinical development involving islatravir due to safety concerns, Merck has recently resumed some islatravir’s development programs while monitoring closely its safety. Furthermore, islatravir is one of the most promising drugs studied in combination with lenacapavir for oral weekly treatment and is investigated in co-formulation with other medicines and in several long-acting technology platforms.