Asthma and COPD are complex diseases with strong genetic and environmental components. These common pulmonary diseases have both different and similar clinical features. Molecular genetic techniques are being used to improve understanding of these common late onset disorders. Recently, several genes and genetic loci associated with increased susceptibility to asthma and COPD have been described. Many of these genes are expressed in the lung tissues, indicating that events in lung tissues might drive disease processes. Lung tissues are rich sources of innate danger signals, and an increased understanding of how the lung tissues communicate with the immune system to maintain healthy tissue might provide new insights into the pathogenesis of chronic inflammatory lung diseases in which injury and repair are in disequilibrium. Given that the innate immune system is at the interface between the airways and environmental insults, genetic polymorphisms in genes related to the innate immune system are likely to affect susceptibility to both asthma and CopD. In addition, some findings from genetic studies provide molecular support for the point of view proposed in the Dutch hypothesis regarding the relationship between asthma and COPD, which highlights the complexity of the pathways that can induce small airway disease and suggests that there is a continuum between asthma and COPD.