Once‑daily antiseizure medication (ASM) regimens improve adherence and reduce treatment burden. This review summarizes the historical development of once-daily ASM therapy, outlined key pharmacokinetic determinants for once‑daily dosing, and proposed practical recommendations for once-daily regimens in routine epilepsy care. Based on pharmacokinetic studies, randomized and observational clinical trials, and expert consensus, the once-daily formulations of commonly used ASMs included older ASMs such as phenobarbital and phenytoin, and the newer generations including zonisamide, perampanel, and cenobamate. In recent years, extended-release (ER) or controlled-release (CR) formulations were produced, e.g., valproate ER, levetiracetam ER, carbamazepine CR, and topiramate ER. Older ASMs such as phenobarbital and phenytoin permit once-daily dosing by virtue of long elimination half‑lives but are limited by narrow therapeutic range, extensive drug–drug interactions, and toxicity. Newer long‑acting agents (zonisamide, perampanel, cenobamate) and ER or CR formulations of established ASMs achieve more stable 24‑hour exposure and smoother peak–trough pharmacokinetics. The once-daily regimen is associated with better adherence, which may in turn support improved seizure control. Bedtime administration with peak concentrations during sleep suited patients with predominantly nocturnal or early‑morning seizures. However, cost and limited availability of newer agents and ER formulations in many lower‑ and middle‑income countries restricted their use despite clear clinical advantages. Once-daily dosing of ASMs is important to enhance adherence, which may help improve seizure control in selected patients.  Clinicians should prioritize once-daily monotherapy where feasible, titrate these ASMs slowly, incorporate therapeutic drug monitoring for narrow‑index drugs, and provide clear counselling on missed doses and behavioral adverse effects.