About one fifth of the world’s population live in South Asia. There are many reasons to be concerned about the impacts of climate change on this region, many parts of which experience apparently intractable poverty. The health problems caused by climate change in South Asia have been conceptualised here as three tiers of linked effects. In this framework, primary health effects are considered the most causally direct impacts of climate change. They include increased mortality and morbidity during heatwaves and ‘natural’ disasters worsened by climate change. Secondary effects include those resulting from ecological changes that alter the epidemiology of some infectious and chronic diseases. Tertiary effects refer to impacts on health of large-scale events with complex, multidimensional economic and political causation, including migration, famine and conflict. Urgent action, both preventive and adaptive, is needed. India, an emerging great power, and the dominant nation in South Asia, must lead urgent and intense engagement with this overarching issue. Transformation of its energy system would improve population health, constitute regional leadership and be significant at the global level.