Chronic Obstructive Pulmonary Disease (COPD) is a major cause of death in the western world and increasing in prevalence in developing countries. COPD is characterised by irreversible airflow obstruction, loss of lung tissue, reduced quality of life and high rates of mortality. The major cause of COPD is tobacco smoke. The changes in the innate immune system directed by tobacco smoke exposure lead to a pronounced and chronic inflammation in the lung. This in turn leads to other pathological changes including remodelling and destruction of lung tissue. Tobacco smoke exposure also leads to infection of the lung by bacteria and viruses. These, bacteria, viruses and co-infection are key triggers of acute worsening's of COPD termed exacerbations. COPD exacerbations are an additional major factor in the morbidity and mortality within COPD and are also the major healthcare costs associated with the disease. Within this review we discuss the response of the immune system to cigarette smoke exposure and inappropriate harmful responses. Successful treatment strategies will need to balance the positive effects of reducing inflammatory aspects of the disease whilst retaining some of the needed immune responses triggered by tobacco smoke exposure.