Epilepsy is a common neurological disorder. Epilepsy has many therapeutic options, the popular one being antiseizure medications. A good proportion of patients always responds well to the existing treatment modalities. But some patients develop resistant epilepsy, and treating them can be challenging with the current treatment; such scenarios are encountered frequently in patients, especially those under treatment for long-term as well as specific syndromes and channelopathies. Resistant epilepsy warrants the need to develop newer therapeutics for better treatment outcomes, and antisense oligonucleotides (ASOs) are one among them. Our review discusses the more recent startups called ASOs in the context of epilepsy therapeutics.