The choice of antiepileptic drugs (AEDs) is rapidly increasing. This review looks at the evidence that guides the decision of which AED to start as monotherapy and aims to aid the choice of treatment if monotherapy fails. Unfortunately, the evidence supporting the prescribing of new drugs is sparse, because most randomised controlled trials answer questions focused on regulatory requirements rather than on clinical use. Ultimately, the choice of one AED will be determined by an individual risk-benefit assessment in which the most effective drug for an individual patient is chosen, and one that would have the lowest risk of significant harm. It is the risk of chronic toxic effects and issues of teratogenicity for women that may affect the choice of drug therapy to the greatest degree. In the future there is a need to improve the quality of clinical data on efficacy and harmful effects of AEDs.