The introduction of combination antiretroviral therapy (cART) has substantially modified the natural history of HIV infection. At the beginning of the cART era the objective was focused on HIV-1-associated mortality and morbidity, but as this objective was accomplished other issues emerged, including toxicity, resistance and compliance with treatment. Moreover, the participation of other disease mechanisms, such as proinflammatory activity, in the so-called non-AIDS events is becoming increasingly important. To overcome these issues, therapeutic options have dramatically expanded, which has made the management of HIV-1-infected patients increasingly complex. The intense changes seen raise the question of what will be the future of HIV infection and its treatment. A projection into the future may help to reflect on current limitations, needs and research priorities, to optimize patient care. To debate on this topic a group of 38 experts has initiated The HIV 2020 Project, with the aim of reflecting on the future of HIV infection and identifying the needs that should be the attention of research in different areas. This document summarizes the group's conclusions on the future of antiretroviral treatment, presented as 20 relevant questions. Each question includes the current status of the topic and our vision for the future.