Severe asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic lung diseases with a clear need for development of new and more efficient therapy. In preclinical research, the mouse model has been instrumental in advancing our knowledge of the biology and immunology. However, it has been proven rather difficult and time consuming to develop new treatments that can impact on the clinical course of these diseases. Many challenges need to be overcome for upgrading the quality of currently available experimental disease models in order to enhance the translation rate of basic research to clinical practice. Establishment of transgenic mouse overexpressing disease-causing genes may provide tools to discover new pathological pathways and to evaluate the possibility of molecular targeted therapy in chronic lung diseases. Personalized medicine, if developed, might be the solution for ‘disease heterogeneity’ and for improving clinical outcome.