The International League Against Epilepsy (ILAE) has recognized the importance of comorbidities in the management of patients with epilepsy. Psychiatric disorders are relatively frequent comorbidities, with a lifetime history identified in one of every three patients and a deleterious impact on quality of life, morbidity, and mortality. However, these problems are, more often than not, ignored, unless they are sufficiently severe to cause major disability. This is due to multiple factors, including patients’ reluctance to volunteer spontaneously information about existing psychiatric symptoms, a paucity (or total lack) of a specific training of the treating neurologist to recognize these psychiatric comorbidities, and a lack of time in busy clinics to screen for them. In general, treatment of psychiatric disorders, especially when sufficiently severe to require hospitalization, should be managed in a psychiatric setting. However, collaboration between psychiatrists and epileptologists is of the essence in the choice of the proper psychotropic drug to avert unnecessary adverse events resulting from their pharmacokinetic and pharmacodynamic interaction with antiepileptic drugs. Such communication can avert the omission of treatment caused by unfounded (although common, alas!) concerns of potential proconvulsant risks associated with psychotropic drugs. Moreover, mild to moderate psychiatric syndrome, especially mild to moderate mood and anxiety disorders, could be managed in epilepsy clinics, thereby simplifying the management of patient and ensuring access to treatment, which is often difficult to find in the community. In the past, different documents have been published under the auspices of the ILAE (Cornaggia et al., 2002) or by ILAE-selected experts (Kerr et al., 2011) discussing the use of psychotropic medications in patients with epilepsy and suggesting treatment options. With this special issue, the ILAE Commission on Neuropsychobiology brought together a number of experts to present pragmatic approaches to the treatment of psychiatric comorbidities. The aim of these articles is to integrate commonly adopted guidance of treatment for psychiatric disorders outside epilepsy to the special needs of people with epilepsy. Two articles address mood and anxiety disorders, and suggest algorithms of treatment in each specific category. The use of antidepressant drugs and the long-lasting misconceptions about seizure worsening are clarified. In addition, psychotherapy approaches are also indicated. One article is dedicated to psychoses of epilepsy, and specific treatment strategies are suggested for specific clinical entities (i.e., interictal psychoses of epilepsy or periictal psychoses). One article discusses the special needs of patients with intellectual disabilities, taking into account the spectrum of behavioral manifestations. Another article is dedicated to the challenging issue of postsurgical psychiatric complications and proposes pragmatic therapeutic approaches. Finally, one article is dedicated to psychogenic nonepileptic seizures (PNES). Obviously, PNES vary in their clinical manifestations and vary in their etiologies; however, standardized therapeutic approaches may be adopted. In conclusion, the relatively high prevalence of psychiatric comorbidities in patients with epilepsy, their negative effect on quality of life, and their association with an increased mortality risk and overall morbidity demand that any clinician treating these patients be familiarized with the recognition and treatment principles of these comorbidities. The Commission on Neuropsychobiology is grateful to the ILAE for its support of the publication of this supplement. The contents of this supplement reflect the opinions of the individual authors and do not necessarily represent official policy or position of the ILAE. MM has received travel grants or consultancy fees from various pharmaceutical companies including Pfizer, UCB Pharma, and Janssen, which are involved in the manufacture of antiepileptic drugs. AMK has received research funding from Pfizer Laboratories. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.