Epilepsy affects more than 70 million individuals of all ages worldwide and remains one of the most severe chronic noncommunicable neurological diseases globally. Several neurotransmitters, membrane protein channels, receptors, enzymes, and, more recently noted, various pathways, such as inflammatory and mTORC complexes, play significant roles in the initiation and propagation of seizures. Over the past two decades, significant developments have been made in the diagnosis and treatment of epilepsy. Various pharmacological drugs with diverse mechanisms of action and other treatment options have been developed to control seizures and treat epilepsy. These options include surgical treatment, nanomedicine, gene therapy, natural products, nervous stimulation, a ketogenic diet, gut microbiota, etc., which are in various developmental stages. Despite a plethora of drugs and other treatment options, one-third of affected individuals are resistant to current medications, while the majority of approved drugs have severe side effects, and significant changes can occur, such as pharmacoresistance, effects on cognition, long-term problems, drug interactions, risks of poor adherence, specific effects for certain medications, and psychological complications. Therefore, the development of new drugs and other treatment options that have no or minimal adverse effects is needed to combat this deadly disease. In this Review, we comprehensively summarize and explain all of the treatment options that have been approved or are in developmental stages for epilepsy as well as their status in clinical trials and advancements.