The characteristic features of chronic obstructive pulmonary disease (COPD) include inflammation and remodeling of the lower airways and lung parenchyma together with activation of inflammatory and immune processes. Due to the increasing habit of cigarette smoking worldwide COPD prevalence is increasing globally. Current therapies are unable to prevent COPD progression in many patients or target many of its hallmark characteristics which may reflect the lack of adequate biomarkers to detect the heterogeneous clinical and molecular nature of COPD. In this chapter we review recent molecular data that may indicate novel pathways that underpin COPD subphenotypes and indicate potential improvements in the classes of drugs currently used to treat COPD. We also highlight the evidence for new drugs or approaches to treat COPD identified using molecular and other approaches including kinase inhibitors, cytokine- and chemokine-directed biologicals and small molecules, anti-oxidants and redox signaling pathway inhibitors, inhaled anti-infectious agents and senolytics. It is important to consider the phenotypes/molecular endotypes of COPD patients together with specific outcome measures to target new therapies to particular COPD subtypes. This will require greater understanding of COPD molecular pathologies and a focus on biomarkers of predicting disease subsets and responder/non-responder populations.