We present a critical perspective of the impact of gender differences on a widely accepted model of ketamine psychosis in healthy volunteers. Male and female patients with schizophrenia present with different symptomatology, disease course and response to pharmacological intervention. Accordingly, it is expected that ketamine psychosis in healthy volunteers fulfils this face validity. Pre-clinical studies in rats indicate a gender difference in response to ketamine administration. However, a review of the literature to date indicates that studies carried out in healthy volunteers have used all male or mixed samples, indicating the need for further studies comparing the psychopathological effects of ketamine in males and females.