AbstractStroke is one of the most common causes of acquired epilepsy, which can also result in disability and increased mortality rates particularly in elderly patients. No preventive treatment for post‐stroke epilepsy is currently available. Development of such treatments has been greatly limited by the lack of biomarkers to reliably identify high‐risk patients. The glymphatic system, including perivascular spaces (PVS), is the brain's waste clearance system, and enlargement or asymmetry of PVS (ePVS) is hypothesized to play a significant role in the pathogenesis of several neurological conditions. In this article, we discuss potential mechanisms for the role of perivascular spaces in the development of post‐stroke epilepsy. Using advanced MR‐imaging techniques, it has been shown that there is asymmetry and impairment of glymphatic function in the setting of ischemic stroke. Furthermore, studies have described a dysfunction of PVS in patients with different focal and generalized epilepsy syndromes. It is thought that inflammatory processes involving PVS and the blood–brain barrier, impairment of waste clearance, and sustained hypertension affecting the glymphatic system during a seizure may play a crucial role in epileptogenesis post‐stroke. We hypothesize that impairment of the glymphatic system and asymmetry and dynamics of ePVS in the course of a stroke contribute to the development of PSE. Automated ePVS detection in stroke patients might thus assist in the identification of high‐risk patients for post‐stroke epilepsy trials.Plain Language SummaryStroke often leads to epilepsy and is one of the main causes of epilepsy in elderly patients, with no preventative treatment available. The brain’s waste removal system, called the glymphatic system which consists of perivascular spaces, may be involved. Enlargement or asymmetry of perivascular spaces could play a role in this and can be visualised with advanced brain imaging after a stroke. Detecting enlarged perivascular spaces in stroke patients could help identify those at risk for post‐stroke epilepsy.