During past decades, knowledge on placental drug metabolism and mechanisms of placental transfer has increased significantly. Most pharmaceutical drugs administered during pregnancy cross the placenta to some extent. The important properties determining the placental transfer by passive diffusion are molecular weight, pK(a), lipid solubility and protein binding. In addition to passive diffusion, compounds may cross the placenta via active transfer, facilitated diffusion, phagocytosis and pinocytosis. This review gives an update of efflux transporter proteins and xenobiotic-metabolizing enzymes that modify the fate and effects of drugs in the placenta.