Drug discovery in epilepsy began with the finding of potassium bromide by Sir Charles Locock in 1857. The following century witnessed the introduction of phenotypic screening tests for discovering antiseizure medications (ASMs). Despite the high success rate of developing ASMs, they have so far failed in eliminating drug resistance and in delivering disease-modifying treatments. This emphasizes the need for new drug discovery strategies in epilepsy. RNA-based drugs have recently shown promise as a new modality with the potential of providing disease modification and counteracting drug resistance in epilepsy. RNA therapeutics can be directed either toward noncoding RNAs, such as microRNAs, long noncoding RNAs (ncRNAs), and circular RNAs, or toward messenger RNAs. The former show promise in sporadic, nongenetic epilepsies, as interference with ncRNAs allows for modulation of entire disease pathways, whereas the latter seem more promising in monogenic childhood epilepsies. Here, we describe therapeutic strategies for modulating disease-associated RNA molecules and highlight the potential of RNA therapeutics for the treatment of different patient populations such as sporadic, drug-resistant epilepsy, and childhood monogenic epilepsies.