High-throughput, genome-wide analytical technologies are now commonly used in all fields of medical research. The most commonly applied of these technologies, gene expression microarrays, have been shown to be both accurate and precise when properly implemented. For over a decade, microarrays have provided novel insight into many complex human diseases. Microarray-based discovery can be classified into three components, biomarker detection, disease (sub)classification and identification of causal mechanism, in order of accomplishment. Within the respiratory system, the application of microarrays has achieved significant success in all components, particularly with respect to lung cancer. Numerous studies over the last half-decade have applied this technology to the characterization of non-malignant respiratory diseases, animal models of respiratory disease and normal developmental processes. Studies of obstructive lung diseases by many groups, including our own, have yielded not only disease biomarkers, but also some novel putative pathogenic mechanisms. We have successfully used an integrative genomics approach, combining microarray analysis with human genetics, to identify susceptibility genes for COPD (chronic obstructive pulmonary disease). Interestingly, we find that the assessment of quantitative phenotypic variables enhances gene discovery. Our studies contribute to the identification of obstructive lung disease biomarkers, provide data associated with disease phenotypes and support the use of an integrated approach to move beyond marker identification to mechanism discovery.