Purpose of reviewPolysubstance use is very common in the world, but there has been limited research in this area. South Asia is sandwiched between two of the world's largest heroin producing areas: the Golden Crescent and the Golden Triangle. The burden and prevalence of polysubstance use have not been estimated in this region of the world. We review the research findings on polysubstance use in different South Asian countries. The review also comments on the gaps in knowledge regarding polysubstance use in this region of the world.Recent findingsThe available literature on polysubstance use from South Asia suggests its widespread presence in the region, ranging from 20 to 90%, more commonly among illicit opioid drug users and injection drug users. Most of the available data is from epidemiological studies. There are few studies on the adverse effects of polysubstance use, but the limited data clearly suggests an elevated risk of comorbid psychopathology and health problems.SummaryPolysubstance use still lacks a consensus definition. There is a need of more research on its prevalence, effects on health, and prevention and treatment.