Airways disease presenting as viral bronchiolitis, asthma and chronic obstructive pulmonary disease (COPD) is an increasingly important source of morbidity in Western Countries. Although these diseases affect distinct age groups, have different initiators and manifest variable amounts of parenchymal remodeling, each process is driven by a common fundamental process involving cellular inflammation. Inflammation is a coordinated multi-cellular response to the presence of pathogens or allergens culminating in altering resident leukocyte populations and remodeling structural tissues in the lung. In this review, we will discuss the contributions of innate and chronic adaptive immunity underlying inflammation seen in bronchiolitis, asthma, both mild and severe, and COPD. We will illustrate how applications of proteomics have begun to provide new insights into critical questions regarding the cellular and innate response to inflammation, role of reactive oxygen stress, identification of phenotypic subgroups using molecular profiling, and how proteomics provides insights into therapeutic responses. We will discuss the available sampling strategies for airway biofluids ( bronchoalveolar lavage, induced sputum, exhaled bronchial breath condensates, and nasopharyngeal aspiration) and the advantages and limitations of each. Selectively applied and properly designed proteomics studies provide an added dimension of information to reduce the impact and burden of these common inflammatory airway diseases.