Currently, there are no established biomarkers which predict the risk of epilepsy following an epileptogenic brain insult, or which predict outcomes of pharmacological or surgical interventions following epilepsy diagnosis. Epilepsy appears to share bidirectional mechanistic relationships with its associated behavioral comorbidities such as neuropsychiatric and cognitive impairments, with several pieces of evidence suggesting that behavioral abnormalities exist before the initial diagnosis of epilepsy. Here, we discuss the preclinical and clinical evidence of these relationships, and the potential for behavioral and cognitive disorders to be harnessed as predictive biomarkers for risk of epilepsy or treatment outcomes.