Severe asthma is a complex heterogeneous disease with substantial unmet clinical need. Understanding the immunopathogenesis is likely to provide insights into potential novel therapies. To date researchers have focussed primarily at a single scale for example genome, cell or whole organ physiology. In this review we shall summarise the current knowledge of the immunopathogenesis of severe asthma integrated across multiple scales to provide the insights into the structure function relationships required to begin to unravel the complexity of severe asthma.