Neurotransmitter transporters play a pivotal role in synaptic transmission: They function as a reset button and thus de?ne the shape and duration of signal transfer across the synaptic cleft. This statement nowadays appears to be a self-evident truism, but the concept is fairly young: It builds on la- mark studies on “reuptake sites” that were done by Georg Hertting and Julius Axelrod about four decades ago. It is, in this context, a special pleasure that Georg Hertting will celebrate his 80th birthday while this volume goes to press. Initially, the pharmacological and biochemical characterization relied on cl- sical organ and tissue preparation techniques as well as on brain homogenates and platelets. This allowed for the characterization of the substrate speci?cities of individual transport processes and the identi?cation of speci?c inhibitors, and it spurred conjecture about the co-transported ions and the stoichiom- ric coupling of ion in?ux and substrate translocation. The impact on clinical medicine of these efforts is best documented by the continuous proliferation of improved—that is, more selective—antidepressant drugs. A major bre- through was achieved by the puri?cation of a prototypical transporter and by themoreorlessconcomitantisolation of cDNAsthatencoded varioustra- porters some 15 years ago. This marked the advent of a new era: What had been an assorted mix of functional activities that was best de?ned by phar- cological criteria was now attributable and accounted for by de?ned molecular species.