Schizophrenia is a serious life-long disease that affects a significant part of the adult population. Although there is considerably effective medication for the positive symptoms of the disease, none are available for the associated cognitive deficits. These deficits are a core feature of schizophrenia, and they severely impair the functionality and social integration of patients. POP is a promising target for the treatment of the cognitive deficits of schizophrenia. Inhibitors of this peptidase show cognition-enhancing properties, act through a complex mechanism and have suitable pharmacological properties. Nevertheless, several studies must be carried out in order to improve the design and clinical evaluation of these substances. Permeability to the brain, appropriate animal models and suitable indications are the main issues that must be addressed. However, current information supports the potential of POP as an interesting drug target for the treatment of the cognitive deficits related to schizophrenia.