The functions of the high-affinity glycine transporters (GLYTs) in vivo have been revealed recently using gene-deletion studies. Results from studies of homozygous knockout mice have reinforced the idea that GLYTs might be specific clinical targets to modulate inhibitory glycine-mediated neurotransmission. In addition, molecular and behavioural analysis of heterozygous mice has confirmed the therapeutic potential of GLYT1 inhibitors in the treatment of several neurological and psychiatric disorders.