Despite the introduction of a host of new antiepileptic drugs (AEDs) over the last 20 years, the older agents, which are potent inducers of the cytochrome P450 (CYP450) system, remain the AEDs most commonly prescribed throughout the world. At the same time, data have gradually and continuously emerged regarding the possible adverse consequences of CYP450 induction, such that it is now appropriate to pose the question of whether the inducing drugs should still be considered first-line agents for the treatment of focal epilepsy. In this article we review the evidence suggesting that these drugs may have many detrimental metabolic effects, along with the data concerning their relative efficacy compared to the newer, noninducing AEDs. We conclude that longer and better-powered studies are needed to truly establish whether the newer AEDs are equivalent in efficacy to the older, inducing agents. Pending this, however, the extant data are sufficiently concerning to suggest that it may be prudent to start with noninducing AEDs unless there is a clear indication for one of the inducing drugs.