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Psychiatric comorbidities are relatively frequent in people with epilepsy (PWE) occurring in one of every three patients, with a predominance of mood and anxiety disorders. Their relation with epilepsy is very complex as not only are patients with epilepsy at greater risk of developing psychiatric disorders, but also those with primary psychiatric disorders are at greater risk of developing epilepsy. The purpose of this review is to identify the implications that this bidirectional relation has on the management of the actual seizure disorder.Psychiatric comorbidities are associated with a worse response to the pharmacologic and surgical treatment of the seizure disorder. In addition, comorbid mood and anxiety disorders have been associated with a worse tolerance of antiepileptic drugs. Furthermore, the complexity between psychiatric comorbidities and epilepsy can also be appreciated in patients with treatment-resistant focal epilepsy who are treated with surgery, as some may experience a remission of presurgical mood and anxiety disorders after surgery, particularly when complete seizure freedom is achieved, whereas others experience an exacerbation in severity during the first 12 months after surgery and others may experience the development of de-novo psychiatric disorders.Psychiatric comorbidities are relatively frequent in PWE and have a bidirectional relation, the consequence of which are reflected in a worse response to the pharmacologic and surgical treatment of the seizure disorder. In addition, the variable changes of presurgical psychiatric comorbidities following epilepsy surgery may be another expression of this complex relation.