Monoamine transporters, such as the dopamine transporter, 5-HT transporter and noradrenaline transporter, in the plasma membrane provide effective control over the intensity of monoamine-mediated signaling by recapturing neurotransmitters released by presynaptic neurons. These proteins represent established targets for several psychotropic drugs, including psychostimulants and antidepressants; however, important issues regarding the selectivity and mechanisms of action of these drugs remain unresolved. Although monoamine transporter knockout mice have profound changes in neurotransmission, they provide useful in vivo models to analyze the effects of psychotropic drugs. In this review, we summarize recent insights into the pharmacology of psychotropic drugs using mice in which the genes encoding these transporters have been deleted.