Epilepsy is a common disease of the nervous system characterized by transient brain dysfunction caused by an abnormal electrical discharge from the brain neurons. The pathogenesis of epilepsy is complex and remains elusive. Nowadays, drug therapy is the mainstay method for the treatment of epilepsy. More than 30 antiseizure drugs (ASDs) were approved for clinical use. Unfortunately, about 30% of patients still display pharmacoresistance against ASDs. The long-term use of ASDs may cause adverse effects, raise tolerability concerns, bring unexpected drug interactions, generate withdrawal symptoms, and increase the economic burden. Thus, the research uncovering more effective ASDs that are safe is still a difficult and urgent task. In this Perspective, we describe the pathogenesis, clinical trials, and drug therapy progress of epilepsy, focusing on summarizing the current situation of small-molecule drug candidates progressing in epilepsy therapy, which provides future directions for the development of more promising ASDs.