Unprovoked seizures are common, affecting approximately 4% of the population by age 80. Only approximately 30% to 40% of patients with a first seizure will have a second unprovoked seizure (ie, epilepsy). Treatment with antiepileptic drugs (AEDs) should not be initiated unless the diagnosis of a seizure is firm. Decisions regarding treatment of single unprovoked seizures must balance seizure recurrence risk, the potential impact of a recurrent seizure, the likelihood of adverse effects of treatment, and patient preference. Risk factors for seizure recurrence include a history of remote neurologic insult, epileptiform abnormalities on electroencephalogram, focal structural lesion on neuroimaging, and family history of epilepsy. Adult patients with these risk factors have a recurrence risk of 60% to 70% and usually should be treated with an AED to prevent seizure recurrence. Without risk factors, the recurrence risk is 20% to 30%, and treatment depends on individual risk-to-benefit ratios and patient preference. Treatment of a first unprovoked seizure is often not necessary in childhood, especially if the seizure is part of a benign self-limited syndrome, such as benign Rolandic epilepsy of childhood. Treatment with an AED reduces the risk of seizure recurrence after a single unprovoked seizure. This must be balanced against the risk of adverse effects of AEDs. Treatment of the first seizure does not appear to affect the long-term prognosis of epilepsy. The choice of an AED should be guided by the seizure type and likely epilepsy syndrome diagnosis. Monotherapy is preferable. Standard AED options include phenytoin, carbamazepine, valproate, and phenobarbital. The newer AED, including gabapentin, lamotrigine, topiramate, oxcarbazepine, levetiracetam, and zonisamide, have good efficacy, favorable pharmacokinetic profiles, and often fewer adverse effects, supporting their use early in treatment. Not all of the newer AEDs are approved for use as monotherapy. Patients with single seizures should be counseled about seizure first aid and general safety measures, including precautions regarding swimming alone, engaging in high-risk activities, driving, possible seizure precipitation by photic stimuli (in generalized epilepsy), sleep deprivation, and alcohol.