Central nervous system (CNS) infections and inflammatory disease are frequent causes of seizures in the intensive care unit (ICU). Given the high incidence of seizures in these disease states, early recognition and treatment can improve patient outcomes, and should be suspected early in the course of evaluation and treatment. Specific infectious causes of encephalitis such as Herpes Simplex Virus (HSV) and Japanese Encephalitis (JE) can present with seizures in up to 34% and 28% of patients, respectively. An infectious etiology is identified in at least 18% of cases of new onset refractory status epilepticus (NORSE). Additionally, there are frequent electroencephalogram (EEG) findings that are characteristic of certain infections, such as lateralized periodic discharges in HSV infections. In some diseases, such as JE, the EEG can also be used as an additional tool to aid in prognosis. Given that many viral and inflammatory illnesses that affect the CNS have no specific treatment, the management of comorbid seizures may be one of the few targets that can effectively improve outcomes.