Arachidonic acid is a polyunsaturated fatty acid that constitutes the phospholipid domain of most cell membranes and is liberated from the cellular membranes by cytoplasmic phospholipase A2 (PLA2). Free arachidonic acid can be metabolized to eicosanoids through three major pathways: the cyclooxygenase (COX), the lipoxygenase (LOX) and the cytochrome P450 monooxygenase pathways. In the COX pathway, the key step is the enzymatic conversion of arachidonic acid to the intermediate prostaglandin G2 (PGG2), which is then reduced to an intermediate PGH2 by the peroxidase activity of COX. PGH2 is sequentially metabolized to prostanoids, including prostaglandins (PGs) and thromboxanes (TXs) by specific prostaglandin and thromboxane synthases. LOXs convert arachidonic acid into biologically active metabolites such as leukotrienes and hydroxyeicosatetraenoic acids (HETEs); P450 metabolizes arachidonic acid into epoxyeicosatrienoic acids (EETs), HETEs and hydroperoxyeicosatetraenoic acids (HPETEs). In the 5-LOX pathway, arachidonic acid is converted to an intermediary 5-HPETE, which is further metabolized to form the unstable leukotriene A4 (LTA4). LTA4 is subsequently converted to 5-HETE, LTB4, LTC4, LTD4 and LTE4. Each of the prostaglandins and leukotrienes exerts its biological effects by binding to its cognate G protein-coupled receptor. PGI2 can transactivate the nuclear peroxisome proliferator-activated receptor-δ (PPARδ), and a PGD2 dehydration product, 15dPGJ2, is a natural ligand for PPARγ. The multidrug resistance-associated protein (MRP) gene family is comprised of efflux transporters for both prostaglandins and leukotrienes, and PGT is an influx transporter for prostaglandins. Hydroxyprostaglandin dehydrogenase 15-(NAD) (15-PGDH) mainly metabolizes intracellular PGE2 and PGF2α to a stable 13,14-dihydro-15-keto-PGE2 and 13,14-dihydro-15-keto-PGF2α. The red boxes indicate the signalling pathways that are discussed in this Review. CysLT, cysteinyl leukotriene; NSAID, non-steroidal anti-inflammatory drug.