Regarding efficacy of new antiepileptic drugs (AEDs) for seizure control, there are three important clinical questions. How effective are new AEDs when corrected for the efficacy of placebo? And even more important: How do new AEDs fare in terms of seizure remission compared with established agents? And finally: Have patients seizure-free on new AEDs a better chance for lasting remission after withdrawal versus those withdrawing from older agents? The answers raise concerns. Although add-on therapy with marketed new AEDs is more effective than placebo, as expected, the treatment difference for becoming seizure-free is disappointingly small (6%; 95% CI: 4–8%; z = 6.47; p < 0.001). Although many, but not all, new AEDs have comparable efficacy to old standard drugs in well-controlled trials, none of the new AEDs is superior to old drugs in terms of seizure remission. So far, we have no antiepileptogenic treatments that prevent the development of epilepsy or modify its detrimental course. The sobering results suggest the need for novel experimental and clinical strategies for the development of more effective new AEDs that interrupt ictogenesis more effectively and prevent or abort epileptogenesis. Ideally, we need new drugs that block both ictogenesis and epileptogenesis, resulting in complete cure of epilepsy.