Numerous advances in our understanding of schizophrenia and its pharmacotherapy have occurred over the last forty years, reflected in basic research endeavours exploring the pathophysiology of schizophrenia, as well as efforts to establish new medications with a more selective psychotropic action and fewer side effects. Ongoing clinical research has, at the same time, provided valuable information regarding the applicability of the various agents, appropriate dosing, symptom response patterns and side effect profiles. This growth in knowledge also has served to underscore the limitations and drawbacks of currently available drugs, leading to a more cautious approach in their use. Newer technologies, such as positron emission tomography, hold considerable promise in our efforts to further clarify the precise mechanisms mediating schizophrenia, and to establish treatment alternatives.