The dopamine (DA) hypothesis of schizophrenia has evolved over the last decade from the stage of circumstantial evidence related to clinical observations and empirical validation from antipsychotic treatment to finally reach more direct testing and validation from imaging studies. These have provided much information that allows us at this point to assemble all the pieces and attempt to synthesize them and integrate them with the other neurotransmitter alterations observed in this illness. Although clearly not sufficient to explain the complexity of this disorder, the DA dysregulation offers a direct relationship to symptoms and to their treatment. We will review here its history, validation, and implications for treatment.