Since much of our knowledge about the neurobiology of schizophrenia derives from the initial discovery that chlorpromazine was effective in treating psychosis, pharmacological research has mostly concentrated on dopamine-blocking agents. Here, the authors discuss the situation where there is no single pharmacological agent on the horizon that could serve as the 'holy grail' to address the full range of symptoms of schizophrenia and what the immediate future holds with the widespread use of polypharmacy.