Tardive dyskinesia (TD) is a movement disorder characterized by abnormal 
involuntary facial movements induced by chronic therapy with classical 
antipsychotic medications. Currently, there is no satisfactory pharmacotherapy 
for TD, which represents a major limitation to therapy with classical 
antipsychotics. In order to develop or optimize therapies for TD, and to develop 
new APDs with lower indices of motor side effects, the pathology underlying TD 
must first be understood. The use of animal models has been used to further this 
objective. Here, we review different preparations that have been used to model 
TD and discuss the contribution of neuroimaging studies conducted in these 
models. Studies in animal models have lead to several hypotheses of TD 
pathology, although none has yet emerged as the ultimate underlying cause of 
this syndrome. We discuss alterations in functional indices, neuron and synapse 
morphology and changes in specific neurotransmitter systems that have been 
described in animal models of TD, and outline how these findings have 
contributed to our understanding of antipsychotic-induced dyskinesias. We 
conclude that several non-mutually exclusive theories of TD are supported by 
animal studies, including increases in oxidative stress leading to structural 
and functional changes in specific neurotransmitter systems. Elucidating the 
mechanisms underlying TD neuropathology partly through the use of animal models 
will lead to the development of APDs with superior side effect profiles or more 
effective therapies for TD.