The nature of causality of mood and psychotic symptoms is complex and evolving. Investigations from different perspectives are under way to elucidate the nature of the origins and maintenance of these disturbances. There is increasing evidence that primary psychotic disorders (bipolar disorder and schizophrenia) are expressions of altered neurobiology. Progress is being made at the genetic and molecular level in the identification of fundamental factors underlying the cause of the major psychotic disorders. Impressive progress has been made at the neurochemical, electrophysiological, and imaging fields.