Diisocyanates are currently the most common cause of occupational asthma in industrialized countries, where its prevalence ranges from less than 5% to 15%. They are mainly used in the production of polyurethane foam, plastic packagings, laminates and polyurethane paints. The diagnosis of diisocyanate asthma is often problematic due to the lack of simple diagnostic or screening tests, uncertainty of underlying mechanisms, and a multitude of other potential occupational and environmental causes of asthma. At present, only a specific standardized challenge test with diisocyanates in concentrations not exceeding the adopted hygiene standards has been found to show a real diagnostic value. The diisocyanate-inducedsensitization, is associated with the recruitment of CD4 T lymphocytes to the lungs and the production of Th2-type cytokines, including IL-4, IL-5 and IL-13. However, clinical studies have suggested that an immunological response to diisocyanates may involve both Th1 and Th2 cells. The development of animal models has been instrumental in furthering the understanding of the pathogenesis of many diseases, including bronchial asthma. Murine models of diisocyanate-induced asthma have proved to be the most useful. Mouse models offer distinct advantages of a better-defined genome than that of guinea pigs or rats and the availability of antibody reagents and transgenic strains to investigate detailed mechanistic pathways. A better understanding of the immunopathogenesis of diisocyanate asthma will hopefully lead to early markers of sensitization and asthma, as well as to a profound comprehension of exposure and host risk factors, both of them should greatly facilitate the development of much-needed diagnostic and preventive strategies for diisocyanate asthma.