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Initiatives are in place to reach super-fast targets by 2018 for paediatric patients living with HIV. However, these efforts are unlikely to be successful until better paediatric antiretrovirals and treatment strategies are available. This commentary reviews the specific features, challenges, and recent developments in paediatric HIV treatment to determine optimal regimen sequencing and use of available drug options. It also outlines a medium and long-term vision for treatment optimization as endorsed by the paediatric antiretroviral drug optimization group.Optimizing antiretroviral therapy (ART) is critical in the context of limited treatment options for children. A first-line dolutegravir-based regimen is the long-term goal for paediatric first-line ART across all age groups. Protease inhibitor-based regimens are expected to continue to play a critical role for second and third-line treatment. New efforts are urgently needed to optimize treatment for children, ensuring access to existing drugs and speeding up development of newer and better formulations moving forward.Over the last few years there have been a number of key developments in paediatric ART which offer the opportunity to reconsider the way ART is optimized for children. Additional evidence is needed to ensure optimal options are available from infancy through adulthood.