Background: Epilepsy affects around 1% of the general population. With already acknowledged strong genetic contributions, >50% of epilepsy cases still remain undiagnosed. This is primordially due to the multifactorial condition of epilepsy that makes it a challenge to select the optimal genetic test for each specific case. Recently, next-generation sequencing (NGS) led to massive gene discovery, including epilepsy that also imposed serious financial burdens on healthcare systems. This study review highlights the progress in the field of epilepsy genetics and argues on how the genetic architecture of common epilepsies is progressively being unraveled. Since the 1995 finding of CHRNA4 mutation, more than 500 genes were estimated to play a significant role in epilepsy. To date, the majority of diagnostic genetic testing is conducted in the pediatric population, while the utility of such testing is less well understood in adults with epilepsy. A broad range in the diagnostic rate of NGS, especially of the Whole Exome Sequencing (WES), in epilepsy has been described. However, NGS introduces new challenges, yet to be resolved. Conclusions: Epilepsy’s genetic background is nowadays undeniable; however, the complexity of this condition makes it difficult to be solved. WES has increasingly been used to uncover the role of the coding genetic material in the human genome and is nowadays considered one of the most costeffective genetic tests for epilepsy, being a prerequisite for personalized treatment approaches and for reducing the epilepsy patient’s “diagnostic odyssey”.