Cystic fibrosis (CF), one of the most common lethal hereditary diseases of white European populations, is caused by loss-of-function mutations in the CF Transmembrane conductance Regulator (CFTR) gene. One of the main causes of mortality is the onset of CF lung disease, which is characterized by chronic infection and inflammation resulting in the progressive remodelling, irreversible damage and fibrosis of the airways. An increasing number of studies indicate that sphingolipids are crucial players in pulmonary manifestations of CF, even if their direct involvement in CF lung disease is still unclear. In this review, we give an overview of the role of sphingolipids in CF pulmonary disease, focusing on the relationship between glycosphingolipids and lung inflammation, which represents the main hallmark of this disease.