Stroke is the leading cause of symptomatic epilepsy in adults, accounting for up to one-third of newly diagnosed seizures among the elderly. About 3% to 5% of stroke patients will suffer a remote seizure, 54% to 66% of whom will develop epilepsy. Thus far, the optimal timing and type of antiepileptic treatment for patients with post-stroke seizure and epilepsy have not been specifically assessed. Although several studies suggest that seizures alter the functional recovery after a stroke, it remains difficult to determine whether or not the occurrence of a second seizure in an untreated stroke patient might hamper the overall outcome. The decision to initiate antiepileptic drug (AED) treatment after a first or a second post-stroke seizure should therefore be individualized, primarily based on the functional impact of the first seizure episode and the patient's preference. Several converging findings suggest that the majority of first-generation AEDs, particularly phenytoin, are not the most appropriate choice in stroke patients because of their potential harmful impact on functional recovery and bone health, their suboptimal pharmacokinetic profile and interaction with anticoagulants or salicylates, their greater likelihood to be poorly tolerated, and the lack of level A evidence regarding their specific use in elderly patients. Among the new-generation AEDs that do not interact with anticoagulants, antiplatelet agents, or bone health, lamotrigine and gabapentine are the only two drugs that proved to be more effective than immediate-release carbamazepine in elderly patients, providing level A evidence for their use in this indication. In addition, gabapentin remains the only drug that has been specifically evaluated in stroke patients, demonstrating a high rate of long-term seizure freedom. At present, low-dose lamotrigine or gabapentin appears to represent the optimal first-line therapy for post-stroke seizure and epilepsy in elderly patients or in younger patients requiring anticoagulants. However, low-dose extended-release carbamazepine might be a reasonable and less expensive option in patients with appropriate bone health who do not requiring anticoagulation.