We explore the magnitude of and current trends in HIV infection among people who inject drugs and estimate the reach of harm reduction interventions among them in seven high-burden countries of the South-East Asia Region. Our data are drawn from the published and unpublished literature, routine national HIV serological and behavioural surveillance surveys and information from key informants. Six countries (Thailand, Myanmar, Nepal, Indonesia, India, and Bangladesh) had significant epidemics of HIV among people who inject drugs. In Thailand, Indonesia, Bangladesh, Myanmar and India, there is no significant decline in the prevalence of HIV epidemics in this population. In Nepal, north-east India, and some cities in Myanmar, there is some evidence of decline in risk behaviours and a concomitant decline in HIV prevalence. This is countered by the rapid emergence of epidemics in new geographical pockets. Available programme data suggest that less than 12 000 of the estimated 800 000 (1.5%) people who inject drugs have access to opioid substitution therapy, and 20–25% were reached by needle–syringe programmes at least once during the past 12 months. A mapping of harm reduction interventions suggests a lack of congruence between the location of established and emerging epidemics and the availability of scaled-up prevention services. Harm reduction interventions in closed settings are almost nonexistent. To achieve significant impact on the HIV epidemics among this population, governments, specifically national AIDS programmes, urgently need to scale up needle–syringe programmes and opioid substitution therapy and make these widely available both in community and closed settings.