A panel of international ICU and epilepsy physicians and researchers detail the epileptic phenomena that occur in the complex environment of the ICU. Focusing on the central nervous system, the authors systematically examine the most up-to-date evidenced-based data regarding ICU seizures, including their most frequent causes, their pathophysiology, their clinical presentation, and the diagnostic evaluation needed to confirm their presence. They also discuss the challenges and specifics of the management of ICU seizures, reviewing the new antiepileptics and their interaction with other ICU medications, drugs with epileptogenic properties used in the ICU, and the role of the new enterally available antiepileptics in treating seizures. Numerous tables summarize drug interactions, neuroimages reveal common ICU seizure etiologies, and multiple electroencephalographic recordings demonstrate clinical or subclinical seizures in ICU patients.