This chapter provides an overview of the known and unknown heritability of the pure epilepsies. The research method used to detect a causal gene variant varies according to the relative risk conferred by the risk allele and its frequency in the population. The considerable progress in identifying genes for Mendelian epilepsy is in sharp contrast to the absence of progress in identifying genetic susceptibility to more common sporadic forms of the disease. The alternative hypothesis to the common variant explanation of a common disease like epilepsy proposes that instead of a few common variants, a large number of rare variants with large effects underlie genetic susceptibility. Exciting developments in very-high-throughput DNA sequencing technology will soon offer the potential for whole-genome resequencing that will ultimately define all the rare variant contributions to epilepsy. The challenge will be how to translate these understandings to better therapies and improved patient care.