About one percent of the world’s population is affected by epilepsy. Epilepsy-induced psychiatric co-morbidity and mortality impose a huge burden on patients, their families, and society. Anti-seizure medications (ASMs) are drugs used to control seizures in patients with epilepsy. Epilepsy constitutes a spectrum of disorders, with various underlying causes. Hence, finding the right drug to control seizures with minimal side effects is a difficult task for clinicians. Besides controlling seizures, many ASMs have off-target effects that result in unwanted side effects. Compared to first and second-generation drugs, third-generation drugs have shown better tolerance. Even though the target of many ASMs is known, their mechanism of action is not well understood. The main mechanism behind epilepsy is defined as an imbalance in the excitatory-to-inhibitory ratio in neurotransmission. So, the key target of ASMs is the ion channels controlling the intrinsic property of neurons like sodium channels, potassium channels, and calcium channels, the excitatory synaptic transmission via glutamate receptors, and the inhibitory synaptic transmission by GABA receptors. Here we review the role of ion channels in epilepsy, and how the ASMs act on them for seizure control.