The striking clinical results from recent studies with Remicade (infliximab, a monoclonal anti-TNFalpha antibody) in rheumatoid arthritis, Crohn's disease and psoriasis demonstrate the disease-altering potential of monoclonal antibodies (mAbs) in chronic inflammation. Chronic obstructive pulmonary disease (COPD) and asthma represent two major chronic pulmonary inflammatory diseases with substantial unmet medical needs. Most of the cells and mediators implicated in the pathophysiology of COPD and asthma are excellent targets for mAb intervention. Indeed, clinical trials with mAbs directed against IL-5, IgE, and CD4 yielded results that are critical in dissecting the pathophysiology of asthma, and reinforce the potential for mAbs as therapeutic agents in treating pulmonary diseases. Furthermore, fundamental advances in the discovery, manufacture and safety of mAbs underscore the enormous therapeutic value of these agents for chronic pulmonary diseases. Indeed, a large number of mAbs are in pre-clinical and clinical development for treating these conditions. In this review, we discuss the scientific rationale for generating mAb therapies directed specifically toward COPD and asthma. We believe that as a therapeutic class, mAbs offer the opportunity to alter symptoms, progression and outcome of chronic pulmonary diseases.