Introduction: Psychiatric comorbidities (such as depression, anxiety, psychosis, inattention, obsession, personality traits, aggression and suicide) are frequent in patients with epilepsy and have a significant impact on medical management and quality of life. Areas covered: A literature search was performed in MEDLINE for epidemiological, longitudinal, prospective, double-blind clinical trial studies published between 1990 and 2011 using the following words: epilepsy, antiepileptic drugs (AEDs), behavioral/emotional/psychiatric comorbidities, suicide and aggression. In this review, the author discusses: i) the characterization and prevalence of behavioral disturbances associated with epilepsy, ii) variables correlated with behavioral comorbidities which include: psychosocial-, clinical-and treatment-related variables, iii) the complex mechanisms of behavioral comorbidities associated with epilepsy, which include both psychosocial (functional) and organic; the process of epileptogenesis, neuronal plasticity, abnormalities in hypothalamic-pituitary axis and neurotransmitters and pathways are fundamental determinants, iv) the negative psychotropic effects of AEDs and their mechanisms and v) the suggested biopsychosocial model of management (pharmacological and non-pharmacological). Expert opinion: The relationship between psychiatric disorders and epilepsy has relevant therapeutic implications which should be directed towards a comprehensive biopsychosocial approach that focuses on the whole person rather than simply on the disease process.