Chronic obstructive pulmonary disease (COPD) is a clinical syndrome that presents as airflow limitation with poor reversibility accompanied by dynamic hyperinflation of the lung. It is a complex disease with chronic inflammatory airway changes caused by exposure to noxious particles or gases, such as cigarette smoke. The disease involves persistent inflammation and oxidative stress, perpetuated by frequent exacerbations. The prevalence of COPD is on the rise, with the prediction that it will be the leading cause of morbidity and mortality over the next decade. Despite the global burden of COPD and its associated morbidity and mortality, treatment remains limited. Although the understanding of the pathogenesis of COPD has increased over the last two decades, molecular approaches to develop new therapies for the treatment of COPD have lagged. Here, we review the molecular approaches that have the potential for developing novel therapies for COPD.