Prostaglandin (PG) E₂ is a well-established lipid mediator that plays a role in diverse functions and diseases of the brain. Cyclooxygenase and PGE synthase have been extensively studied as molecular determinants of extracellular concentration of PGE₂ near prostanoid E receptors since the brain has limited capacity of PG metabolism. There is accumulating evidence that several members of the solute carrier (SLC) and ATP-binding cassette (ABC) superfamilies regulate PGE₂ distribution in brain capillary endothelial cells, choroid plexus (CP) and arachnoid epithelium, and different parenchyma cells such as neuronal and glial cells. These transporters may mediate entry and exit of PGE₂ at blood–brain and blood–cerebrospinal fluid boundaries, resulting in brain distribution of PGE₂. However, their roles in neuroinflammation and disease progression remain unclear. In this review, current knowledge on transporters involved in brain distribution of PGE₂ is summarized, and especially, potentials of organic anion transporting polypeptide (OATP) and organic anion transporter (OAT) family members are discussed as molecular determinants of PGE₂ concentration in the brain.