Described over a century ago, schizophrenia still presents personal, clinical and scientific challenges, and is increasingly considered a concept rather than a single disorder. It has become a paradigmatic psychiatric disorder while remaining something of an enigma. Defined by a syndrome of psychotic phenomena (positive phenomena such as delusions, hallucinations or disordered thought structure) and negative features resulting from motivation and emotional dysfunction, schizophrenia is defined by symptoms lasting at least 4 weeks and impairment for 6 months or more [1, 2]. Where the illness is short-lived, the clinical syndrome is defined as a schizophrenia-related diagnosis [1]. The clinical presentation usually encompasses features prominent in other psychiatric conditions such as cognitive dysfunction, motor abnormalities, obsessional phenomena or depression. These additional features not included in the definition of schizophrenia underscore its pervasive neural dysfunction; they influence management and often shape the clinical outcome. The seeds of schizophrenia may be sown in early life with aberrant childhood development in multiple domains [2], but the clinical syndrome typically presents in early adulthood (Figure 9.10.1); abnormal neural connectivity may underly these seemingly remote phenomena.