Despite major advances in neuroimaging, no lesion is visualized on MRI in up to a quarter of patients with drug-resistant focal epilepsy presenting for presurgical evaluation. These patients demonstrate poorer surgical outcomes than those with lesion seen on MRI. Accurate localization of the seizure onset zone (SOZ) is more difficult in MRI-negative patients and often requires invasive EEG recordings. Positron emission tomography (PET) and magnetoencephalography (MEG) have been proposed as clinically relevant tools to localize the SOZ prior to intracranial EEG recordings. However, there is no consensus regarding the optimal gold standard that should be used for assessing the performance of these presurgical investigations. Here, we review the current knowledge concerning the usefulness of PET and MEG for presurgical assessment of MRI-negative epilepsy. Beyond the individual diagnostic performance of MEG and of different PET tracers, including [(18)F]-fluorodeoxyglucose, [(11)C]flumazenil, and markers of 5-HT1A receptors, recent data suggest that the combination of PET and MEG might provide greater sensitivity and specificity than that of each of the two individual tests in patients with normal MRI.