Sphingolipids such as sphingosine-1-phosphate (S1P), ceramide or sphingomyelin are essential constituents of plasma membranes and regulate many (patho)physiological cellular responses inducing apoptosis and cell survival, vascular permeability, mast cell activation and airway smooth muscle functions. The complexity of sphingolipid biology is generated by a great variety of compounds, diverse receptors and often antagonistic functions of different sphingolipids. For instance, apoptosis is promoted by ceramide and prevented by S1P, and pulmonary vascular permeability is increased by S1P_2/3-receptors and by ceramide, while S1P₁-receptors stabilize barrier integrity. Several enzymes of the sphingolipid metabolism respond to external stimuli such as sphingomyelinase isoenzymes that are activated by many stress stimuli and the sphingosine kinase isoenzymes that are activated by allergens. The past years have provided increasing evidences that these processes contribute to pulmonary disease such asthma, COPD, acute lung injury and cystic fibrosis. The sphingolipid metabolism offers several novel therapeutic targets for the treatment of lung diseases such as emphysema, asthma, cystic fibrosis, respiratory tract infection, sepsis and acute lung injury.