There has been an increased interest recently in various Drosophila models of human disease. The goals are to uncover the fundamental biological principles underlying causes and cures of human pathology utilizing the power of Drosophila genetics. A particularly exciting prospect is that new therapeutics could be forthcoming through identification of disease-causing genes followed by targeted drug development or by the development of platforms for high-throughput drug screening. This chapter reviews a model of human epilepsy based on a set of seizure-sensitive Drosophila mutants that exhibit features resembling some human epilepsies. Especially interesting are descriptions of a novel class of mutations that are second-site seizure-suppressor mutations. These mutations revert epilepsy phenotypes back to the wild-type range of seizure susceptibility. The genes responsible for seizure suppression are cloned with the goal of identifying targets for lead compounds that may be developed into new anti-epileptic drugs (AEDs).