The advent of new antiepileptic drugs (AED) has increased the opportunities for interaction. Clinicians seek therapeutic interactions in which two AED together have greater efficacy than either drug alone; there are case reports of such, but few prospective studies. Interactions must also be suspected when the adverse effects of a new AED differ according to the co-medication. The basis can be pharmacodynamic, but more frequently it is pharmacokinetic. Inhibition of cytochrome P450 enzymes by the new drugs is more common than induction. There are important implications for the design of clinical trials and the planning of treatment changes in patients.