Several lines of investigation have contributed to the increasing recognition of the biological basis of psychiatric disorders. Symptom provocation studies have made important contributions toward this. With the emergence of novel methodologies, the role of symptom provocation studies has come under increasing scrutiny and debate. The scientific contributions and risks of symptom provocation studies are discussed using the psychostimulant paradigm in schizophrenia research as the prototypical study. The application of studies in other areas of medicine that carry risks similar to those associated with symptom provocation studies, are also reviewed. The authors draw on the parallel of cardiac stress testing to highlight risks: benefits issues. Finally, the authors discuss the future of symptom provocation studies and emphasize that these studies will need to meet the highest scientific standards, ethical standards and safeguards.