Plasma membrane transporters terminate the actions of several small molecule neurotransmitters, including glutamate, gamma-aminobutyric acid, glycine, dopamine, serotonin and norepinephrine. The fact that anti-depressants, cocaine and amphetamines can have such profound behavioral effects by inhibiting the activity of some of these transporters underscores the importance of these molecules. Recent studies have begun to define the mechanisms that regulate these transporters. As these studies progress, it is becoming clear that the transporters form complexes both with themselves and with many other proteins that can regulate either transporter localization or activity. In most cases, the physiological and/or pathological relevance of these interactions is only beginning to emerge.