The broad application of next-generation sequencing in genetic diagnostics opens up vast possibilities for personalized treatment of patients with genetic disorders including monogenic epilepsies. To translate genetic findings into personalized medicine, mechanistic studies of the individual pathogenic variants and drug screening in patient-specific in vitro models are very crucial. Recently, human induced pluripotent stem cell (hiPSC) technologies have made it possible to generate patient-specific pluripotent cells, which can be directed to differentiate into any given cell type. These hiPSCs are ideal for generating neurons to investigate specific neurological/neurodevelopmental disorders. While two-dimensional single-cell models of hiPSC-derived neurons provide reliable investigation of synaptic transmission and plasticity, cerebral organoids are superior in regard to functional characterization and the study of cell-cell interactions in three-dimensional structures. In this review, we focus on monogenic epilepsies and discuss the application of hiPSC models in personalized drug treatment based on the patient’s specific genetic variants.