New antiretrovirals (ARVs), particularly the potentially “game-changing” ARV dolutegravir, offer major potential to meet the compelling need for simpler and better HIV treatment for tens of millions of people in the coming decade. Advantages include substantially lower manufacturing cost, fewer side effects, and less risk of resistance. But key obstacles must be addressed in order to develop and introduce new ARVs in specific combinations optimized for the needs of low- and middle-income countries. Strong leadership will be essential from the global health community to nurture more focused collaboration between the private and public sectors.