Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by airflow limitation. It is predicted to become the third leading cause of death in the U.S. by 2020. The advancement of this disease is not fully reversible. Among others, exposure to cigarette smoke (CS) leads to abnormal inflammatory responses in the lungs. Second-hand cigarette smoke (SHS) exposure is considered to be a risk factor associated with increased carriage of respiratory pathogens and frequent airway infections. Generally, such association is ascribed to immunomodulatory and irritant effects of the components of CS (in human cells). The toxic response can be individual or in combination with other agents, including among others bacteria. Epidemiological evidence has shown that nontypeable-Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa are the most common forms of bacteria that colonize in the COPD airway. These agents and other inhaled particles are effectively eliminated by alveolar macrophages and airway and lung epithelial cells which sense them. Interestingly, secondhand smoke exposure activates these cells to produce pro-inflammatory mediators, reactive oxygen species and proteolytic enzymes, thereby providing a cellular mechanism that links smoking with inflammation and tissue damage. During COPD these cells are exposed either frequent or prolonged periods of time to a host of inflammatory mediators and effector molecules from inflammatory cells. Impairments in innate lung responses in patients with COPD mediate exacerbations by enabling bacteria to proliferate and persist in the airways. Persistence of bacteria leads to chronic airway inflammation, which is enhanced during invasion by incoming bacterial pathogens. Therefore, development of novel therapeutic approaches that lead to rapid and successful elimination of pathogenic bacteria from COPD airways, and reduce the mortality rate of COPD (high) are urgently needed.