Schizophrenia (SZ) remains the most challenging psychiatric pathology at moment despite huge efforts made with the scope to achieve a clear better understanding of its etiology and pathophysiology. at least 1% of world populations suffers from this disease.

An avalanche of recent studies reveals the massive importance of glutamate abnormalities which appear in the debut phases and contribute essentially to the further development of severe symptoms. Old, classical and peculiar dopamine hypothesis starts day by day to become less feasible.

Based on a better understanding will be more efficient to develop more efficient therapeutic products. Based on more accuracy and real understanding of GABA and Glutamate roles in the pathophysiology of SZ is possible for staring more efficient therapies

In this sense we realised a thematical research study from vast bibliographical resources.between 2000–2009 all basic research and clinic-pathological studies, indexed on Pubmed, Medline and Wiley Science Library had been reviewed.

Simple mechanical appreciation shows, unfortunately, that at moment dopamine theory still dominates the etio-pathology of this major psychiatric syndrome. In fact dopamine variations are secondary to glutamate dysfunctions. We don’t need to forget that most of actual treatments-second generation of antipsychotics- had been produced on basis of dopamine hyperfunction theory. The importance of glutamate and GABA deficiencies, which offer a more clear and logical explanation of pathology seen in SZ, cannot be considered as secondary to hypodopaminergic frontality or to hyperdopaminergic inputs from nucleus accumbens.