The concept of using gene-environment studies to discover mechanisms of asthma in early life is deceptively simple and attractive. To do so would appear to require a straightforward examination of relationships between a polymorphism and asthma-related phenotypes in young children. However, in reality, the process is far from simple and lack of appreciation of the complexity of this area of research has been one of the reasons for such slow progress. To understand current knowledge of gene-environment interactions in early life requires insight into environmental factors that have been associated with early-onset asthma. Gaining such insight is difficult because the critical environmental factors that are causally associated with asthma at this stage are still unclear. This article discusses known environmental and epidemiological factors, along with examples of gene-environment interactions, followed by a general discussion of problems with current studies and a description of newer approaches being used to make progress in this complex area.