The mammalian placenta acts at the interface between maternal and fetal circulatory systems, regulating the transport of molecules in both directions. Part of this gatekeeping function is provided by ABCB1, a drug efflux transporter that protects the fetus from accumulation of hundreds of xenobiotics (both endogenous and exogenous). ABCB1 expression shows a circadian rhythm in placenta and other tissues, but whether this rhythm depends on the local circadian clock remains unknown. Now, Cécile Demarez, Mariana Astiz and colleagues address this question, first showing the presence of the circadian clock in the labyrinth zone (LZ) of the mouse placenta. The LZ (a fetal-origin tissue functionally analogous to the human chorionic villi) shows rhythmic 24h expression profiles for some clock genes, as well as for Abcb1a/b. The authors demonstrate, for the first time, that the circadian rhythm of Abcb1a/b expression and activity is controlled by the local clock in the LZ, specifically in the LZ trophoblast layer. An important consideration that follows from this work is that the fetal efficacy or toxicity of more than 300 different xenobiotics that are substrates of ABCB1 will be influenced by the time of day of treatment.