The brain potential known as mismatch negativity (MMN) is one of the most studied indices of altered brain function in schizophrenia. This review looks at what has been learned about MMN in schizophrenia over the last three decades and why the level of interest and activity in this field of research remains strong. A diligent consideration of available evidence suggests that MMN can serve as a biomarker in schizophrenia, but perhaps not the kind of biomarker that early research supposed. This review concludes that MMN measurement is likely to be most useful as a monitoring and response biomarker enabling tracking of an underlying pathology and efficacy of interventions, respectively. The role of, and challenges presented by, pre-clinical models is discussed as well as the merits of different methodologies that can be brought to bear in pursuing a deeper understanding of pathophysiology that might explain smaller MMN in schizophrenia.