Psychosurgery refers to the surgical interruption of the white matter fibres joining the frontal cortex to the remainder of the cortical mantle and to the thalamus, in an attempt to mitigate the manifestations of psychosis. It reached its heyday following World War Two and was abandoned with the introduction of major tranquilisers such as chlorpromazine. Wilder Penfield, unlike most of his contemporaries, had a jaundiced view of psychosurgery. This paper addresses Penfield’s early experience with experimental, penetrating brain trauma and with the surgical resection of frontal, epileptogenic lesions, which explain his antagonism towards psychosurgery.