Comorbid health conditions are common among people with epilepsy. Proposed explanations for this association include the possibility that first, epilepsy (including its treatment) causes the comorbid condition; second, the comorbid condition (including its treatment) causes epilepsy; or third, a common pathogenic mechanism mediates the co-occurrence of epilepsy and the comorbid condition. It is unlikely that a single explanation will suffice for all of the epilepsy comorbid conditions. Determining the basis of the association between epilepsy and its comorbid conditions has important implications for diagnosis and management. In this paper, we discuss this issue in the context of five common epilepsy comorbid conditions: bone health and fractures, stroke, depression, migraine and attention-deficit hyperactivity disorder. Current findings, research limitations and future directions of research efforts are discussed.