Epilepsy is still an issue that perplexes the epileptologists worldwide, with a reported impact on 50 million populations. With the reconceptualization of epilepsy as a disease of brain networks, it is great timing to rethink epilepsy and those associated comorbidities, including cognitive and behavioral comorbidities, psychiatric comorbidities, cardiovascular disease and migraine. In this review, we introduce the state of the art of these comorbidities of refractory epilepsy, including etiology, epidemiology, manifestation and mechanism. As essential comorbidities of epilepsy share the network consistent with epilepsy, a series of recent studies of comorbidities of epilepsy supply a new perspective on epileptic network. It is possible to accelerate the progression of epilepsy by translating those exciting advances in epileptic network into routine clinical practice.