Efforts to define the mechanisms governing neurotransmitter uptake and drug action have moved into high gear with the publication of a high-resolution structure of a leucine transporter from Aquifex aeolicus, a bacterial member of the SLC6 transporter family. Solved with the substrate leucine bound, the new structure corroborates extensive biochemical and mutagenesis studies performed with related mammalian neurotransmitter transporters and provides exciting suggestions as to how coupling arises between ions and substrates to permit efficient neurotransmitter clearance.