Neurotransmitters are chemical messengers by which neurons communicate with each other. High affinity uptake of neurotransmitters is mediated by transporter proteins and is the most common mechanism for the termination of neurotransmitter signaling. Transporters clear neurotransmitters not only to control the timing of neurochemical communication, but also to recapture transmitter molecules for later reuse. In addition to their obvious and critical role in neurotransmitter homeostasis, transporters are also important targets for therapeutic drugs as well as drugs of abuse and known neurotoxins. Here, we summarize the mechanism of transporter function, how transporter protein structure defines the functional properties of transporters, the cellular signals, and determinants that regulate transporters, and how disease states are related to neurotransmitter transporter dysfunction.