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Nonlesional focal epilepsies (nlFE) represent a heterogenous group of syndromes. They encompass self-limited focal epilepsies of childhood and youth, rare focal, familial epilepsies, epilepsies associated with brain somatic variants, and to a large extent nonfamilial epilepsies that have a complex genetic or unknown background. Genetic testing should be performed in cases of a family history suggestive of monogenic inheritance and in cases that show additional symptoms, such as intellectual impairment, autism, or dysmorphic features. Whole-exome or whole-genome sequencing is the method of choice. Growing evidence suggests including genetic testing also in the presurgical workup of individuals with drug-resistant epilepsy. While individuals that harbor variants in genes of the mammalian target of rapamycin (mTOR) pathway tend to achieve better seizure control following epilepsy surgery, the postsurgical outcome of genetic epilepsies associated with channel function or synaptic transmission appears to be poor. The aim of this article is to review the genetic background of focal epilepsies that occur or persist in adults, provide guidance for genetic testing, and discuss potential implications for presurgical evaluation.