Prostaglandins (PGs) and leukotrienes (LTs) are important proinflammatory mediators. They are both derived from arachidonic acid (AA). Cyclooxygenase (COX), the key enzyme in transforming AA into PGs, has two isoforms: COX-1 is constitutively expressed, and COX-2, is inducible. Lipoxygenase (5-LO) is the key enzyme for LT production. PGs and LTs have been intensively studied. Release of these molecules is associated with mucus secretion, redness, pain, fever and other inflammatory manifestations. Both PGs and LTs are involved in host defense against various pathogens. In addition to mediating inflammatory symptoms, PGs might suppress some innate immune factors, including nitric oxide (NO) production. PGs also suppress a TH1 response. LTs have pathologic potential, especially in asthma. LTs also have been found to have positive roles in host defense, either against virus or bacteria. Finally, PGs and LTs might regulate the production of each other, possibly at the level of substrate competition by their enzymes. Because they are clinically important molecules, a further understanding of the roles that PGs and LTs played in host defense will have great impact on therapeutic research.