Global access to deworming treatment is one of the public health success stories of low-income countries in the 21st Century. Parasitic worm infections are among the most ubiquitous chronic infections of humans, and early success with mass treatment programmes for these infections was the key catalyst for the Neglected Tropical Disease (NTD) agenda. Since the launch of the “London Declaration” in 2012, school-based deworming programmes have become the world’s largest public health interventions. WHO estimates that by 2020, some 3.3 billion school-based drug treatments had been delivered. The success of this approach was brought to a dramatic halt in April 2020 when schools were closed worldwide to minimize COVID-19 pandemic transmission. These closures immediately excluded 1.5 billion children not only from access to education but also from all school-based health services, including deworming. WHO PULSE surveys in 2021 identified NTD treatment as among the most negatively affected health interventions worldwide, second only to mental health interventions. In reaction, governments created a global Coalition with the twin aims of reopening schools and of rebuilding more resilient school-based health systems. Today, some 75 countries, comprising more than half the world’s population, are delivering on this response, and school-based coverage of some key school-based programmes exceeds 2020 levels. This paper explores how science, and a combination of new policy and epidemiological perspectives, led to the exceptional growth in school-based NTD programmes after 2012, and are again driving new momentum in response to the COVID-19 pandemic.