The advent of multiple new antiepileptic drugs (AEDs) in the past 15 years has provided new options for clinicians treating patients with epilepsy, but has also created a need for guidelines in AED use. For selection of the most appropriate AED, the neurologist must know the pharmacological properties of the AEDs and has to balance their benefits and potential risks for the individual patient. A key consideration in AED selection is spectrum of efficacy for seizure types and epileptic syndrome. Other factors in AED selection include safety and tolerability, ease of use and titration rate, potential interactions, and efficacy in coexisting nonepileptic conditions. Comorbid conditions may favor or exclude the use of certain AEDs in a particular patient. Special considerations apply in specific epilepsy populations, such as women of childbearing age, children, and the elderly. This article analyzes the various factors involved in choosing an AED.