This chapter is an update on the dopamine (DA) imbalance in schizophrenia, including the evidence for subcortical hyperstimulation of D2 receptors underlying positive symptoms and cortical hypodopaminergia-mediating cognitive disturbances and negative symptoms. After a brief review of the anatomical neurocircuitry of this transmitter system as a background, we summarize the evidence for dopaminergic alterations deriving from pharmacological, postmortem, and imaging studies. This evidence supports a prominent role for D2 antagonism in the treatment of positive symptoms of schizophrenia and strongly suggests the need for alternative approaches to address the more challenging problem of negative symptoms and cognitive disturbances.