Status epilepticus (SE) is a medical emergency with high mortality rate. Common causes of SE include noncompliance with antiepileptic medications, drug- and alcohol-related etiologies, and central nervous system (CNS) infections. Because prolonged seizures can cause neuronal damage, treatment should be initiated promptly to avoid potential complications. Previous studies support intravenous (IV) lorazepam as first-line therapy and IV phenytoin or fosphenytoin as a second-line medication. If first-and second-line medications fail to control SE, further treatment with propofol, pentobarbital, midazolam, or other medications should be considered. Many of the drugs currently used to control SE are associated with sedation, respiratory suppression, hypotension, cardiac dysrhythmia, and anaphylactic reactions. Therefore, IV valproate or other newer antiepileptic drugs may be considered as an alternative third-line therapy for those who cannot tolerate the hypotensive effects of other anticonvulsants. This paper reviews comparative effectiveness and safety concerns among frequently used medications for SE.