The development of asthma in an individual depends upon the interaction of genetic factors with the environment. Asthma is a polygenic disease and both genome screening and candidate gene strategies have identified a number of putative genes that may predispose to the development of asthma. However, there are few data regarding genes that may either dictate disease severity or chronicity and genes that dictate response to treatment. Analysing asthma as a categorical variable will fail to identify genes solely involved in determining disease severity, whereas studies designed to analyse asthma as a semiquantitative trait may identify these genes in addition to disease-initiating genes. However, identifying genes specifically involved in the determination of disease severity (e.g. in airway remodelling) will be ideally performed in cohorts of asthmatics specifically recruited and using appropriate end points. This review discusses methodological issues concerned with identifying disease-modifying genes in individuals with asthma, and summarizes the potential contribution of known candidate genes to the determination of disease severity.