Our analysis of experience from programmes targeting malaria, leprosy and TB shows the importance of drawing broadly on research and implementation expertise, and civil society more broadly, when setting targets for HIV control. The engagement of stake-holders from the highest burden settings, including affected populations, is crucial, to ensure that disease control efforts uphold human rights and tackle HIV-related stigma and discrimination. An appropriate balance is needed between ambitious, galvanising global targets that drive funding and political/public engagement, and targets that reflect the complexities and local epidemiological variations in disease profile. Ethical issues and unintended consequences need to be considered when setting targets—particularly around local effects and opportunity costs of having foregone other areas of disease control and public health. Intermediate and adaptable targets are needed that allow for course corrections to programmes. Overly burdensome reporting requirements for individual local programmes and countries should be avoided, as well as potential for overlapping and sometimes conflicting targets both within and across vertical disease programmes. Process targets should be distinguished from outcome targets, which should be measurable and based on high-quality data. Retention of expert healthcare worker skills and specialist services is vital, while moving towards integrated health systems if effective disease control programmes are to be maintained. Target development should seek areas of programme delivery where an opportunity to codevelop targets and integrate services exists. Global efforts to move to universal health coverage (UHC), for example, could be factored in when developing targets. Sustaining investment and continuing political interest in the end phase of any elimination or eradication strategy, once incidence and prevalence are low, are critical to achieve success. Equity-and access-based service delivery targets become increasingly important as the elimination strategy nears its end and should be factored into planning. Achieving disease elimination and/or eradication is only possible with sufficient investment in research to develop new prevention tools such as vaccines, point-of-care diagnostics, and treatments to counteract the effects of increasing drug resistance and the challenging latency period of diseases; public health infrastructure upgrades that address wider determinants of health; and health and surveillance systems that allow for equitable delivery and access to services.