AbstractApart from seizure freedom, the presence of comorbidities related to neurological, cardiovascular, or psychiatric disorders is the largest determinant of a reduced health‐related quality of life in people with epilepsy (PwE). However, comorbidities are often underrecognized and undertreated, and clinical management of comorbid conditions can be challenging. The focus of a comprehensive treatment regimen should maximize seizure control while optimizing clinical management of treatable comorbidities to improve a person's quality of life and overall health. A panel of four European epileptologists with expertise in their respective fields of epilepsy‐related comorbidities combined the latest available scientific evidence with clinical expertise and collaborated to provide consensus practical advice to improve the identification and management of comorbidities in PwE. This review provides a critical evaluation for the diagnosis and management of sleep–wake disorders, cardiovascular diseases, cognitive dysfunction, and depression in PwE. Whenever possible, clinical data have been provided. The PubMed database was the main search source for the literature review. The deleterious pathophysiological processes underlying neurological, cardiovascular, or psychiatric comorbidities in PwE interact with the processes responsible for generating seizures to increase cerebral and physiological dysfunction. This can increase the likelihood of developing drug‐resistant epilepsy; therefore, early identification of comorbidities and intervention is imperative. The practical evidence‐based advice presented in this article may help clinical neurologists and other specialist physicians responsible for the care and management of PwE.