Chronic obstructive pulmonary disease (COPD) includes a spectrum of conditions that have in common varying degrees of airflow obstruction, such as chronic bronchitis and emphysema. There is an increasing evidence of involvement of sphingolipids as key molecular mediators or biomarkers of disease in emphysema, chronic bronchitis, and more recently in asthma, another disease characterized by (reversible) airflow obstruction. Given the recognized central role of oxidative stress and inflammatory stimuli along with involvement of immune responses, apoptosis, and tissue remodeling in the development of chronic obstructive lung diseases, it is not surprising that sphingolipids have been shown to play important role in their pathobiology. In particular the pro-apoptotic effects of ceramide were suspected as events in the lung destruction that occurs as a result of apoptotic loss of structural cells comprising the alveolar walls, such as microvascular endothelial cells and alveolar epithelial cells. In addition, the role of ceramide was investigated in models of larger airway epithelial cell stress responses to cigarette smoke, in the context of ensuing airway remodeling and inflammation. This chapter discusses current evidence of sphingolipid perturbations in experimental models of COPD and relevant links to human disease based on translational and epidemiological data.