The term hemispheric malformations of cortical development (MCDs) is used in this article to represent congenital malformations that predominantly or exclusively involve complete or substantial portion of one cerebral hemisphere. Hemispheric MCDs usually present during early childhood with intractable epilepsy, cognitive delay, and contralateral hemiparesis. Early identification and selection of children who may be candidates for epilepsy surgery are important during diagnostic evaluation of hemispheric MCD. Surgical intervention at an appropriate time, whenever possible, offers the best chance for seizure freedom and improved cognitive outcome. In addition, making an accurate genetic diagnosis is imperative to offer genetic testing and counseling to the family. In this article, the authors discuss the developmental and genetic mechanisms, pathologic features, diagnosis, and treatment of hemispheric MCD that are substrates of catastrophic childhood epilepsy amenable to surgical treatment.