SARS-CoV-2, the virus that causes COVID-19, has changed the world as we know it, and continues to do so. How COVID-19 affects people who use drugs, the environments in which they live, and capacities of response, warrants immediate attention. This special issue begins to map how COVID-19 is altering the health of people who use drugs, including in relation to patterns of drug use, service responses, harms that may relate to drug use, interventions to reduce risk of harms, COVID-19 health, and drug policies. We emphasise the need to envisage COVID-19 and its effects as a matter of intersecting ‘complex adaptive systems’: that is, the impacts of COVID-19 extend beyond the virus and related illness conditions to encompass multiple social, cultural, economic, policy and political effects; and these affect the health of people who use drugs directly as well as indirectly by altering the risk and enabling environments in which they live. We synthesize emergent evidence on the impact of COVID-19 on the health of people who use drugs. A key concern we identify is how to sustain policy and service delivery improvements prompted by COVID-19. We need to maintain an ethos of emergent adaptation and experimentation towards the creation of safer environments in relation to the health of people who use drugs.