Lysophosphatidic acid and sphingosine 1-phosphate are structurally simple and physiologically very important lysophospholipids. Because they possess distinct structural backbones (glycerol and sphingosine, respectively), there are different metabolic pathways for their intracellular production. Recently, several key enzymes that produce or degrade these lysolipid phosphate mediators extracellularly have been characterized. This review focuses on the physiological and pathophysiological significances of the extracellular metabolic pathways involving recently characterized exo-type lysophospholipase D, ecto-type phospholipase A, and ecto-type lipid phosphate phosphatase.