Glutamatergic and dopaminergic systems play a primary role in frontal-subcortical circuits involved in motor and cognitive functions. Considerable evidence has emerged indicating that the complex interaction between these neurotransmitter systems within the dorsal striatum and nucleus accumbens is critically involved in the gating of information flow in these highly integrative brain regions. As a result, disruptions of the interaction between glutamate and dopamine has been proposed as a pathological basis for a number of disorders, including the pathophysiology of schizophrenia. In this chapter, we discuss recent studies that have significantly advanced our understanding of the reciprocal interactions between glutamatergic and dopaminergic systems within the striatal complex in the normal brain and in pathological states.