The predominant hypothesis regarding the pathophysiology of schizophrenia is that it is associated with impaired dopamine neurotransmission. The mesolimbic pathway originates from the midbrain ventral tegmental area and innervates the ventral striatum (nucleus accumbens), olfactory tubercle, and parts of the limbic system. The mesocortical pathway, also originating from the midbrain ventral tegmental area, innervates areas of the frontal cortex and has been implicated in learning and memory. Overactivity of the mesolimbic pathway has been implicated in the development of the positive symptoms of schizophrenia. The negative and some cognitive symptoms have been associated with a reduction of dopamine activity in the mesocortical pathways together with a hypostimulation of dopamine receptors in the prefrontal cortex. There are 2 overall goals of treatment: (1) to reduce the activity of hyperactive pathways mediating psychosis and (2) to increase the activity of hypoactive pathways that seem to mediate negative and cognitive symptoms, while simultaneously preserving the activity of the pathways that regulate motor movement and prolactin secretion. There is also a putative interrelationship between N-methyl-D-aspartate (NMDA) hypofunction and dopamine (DA) dysregulation and these processes may be linked to the pathogenesis of schizophrenia. It has been postulated that NMDA hypofunction in the prefrontal cortex and its connections may result in a pattern of dopamine dysregulation. In the prefrontal area, this pattern consists of a dopamine deficit and a hypostimulation of D1 receptors that are linked to the appearance of negative symptoms and cognitive impairment. However, at the subcortical level, NMDA hypofunction results in dopamine excess, hyperstimulation of D2 receptors, and the appearance of positive symptoms. It has also been suggested that the prefrontal dopamine deficit and the subcortical dopamine excess feed back, in turn, to the NMDA circuitry. In addition there is evidence that the deficit in cortical dopamine may also be linked to the generation of a subcortical dopamine excess. There is a complex modulation of dopamine by different serotonergic receptor systems as well as by nicotinic receptors. These may be additional sites for effects of antipsychotics. This conference tries to underline the current possible scientific basis for the use of atypical antipsychotics.