This review aims to synthesize all the available data on brain molecular imaging, such as single-photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose positron emission tomography (FDG-PET), in focal epilepsies. SPECT imaging is able to measure regional cerebral blood flow and its major innovation remains its ictal imaging value. On the other hand, FDG-PET, which has higher spatial resolution and lower background activity than SPECT, enables glycolytic metabolism to be identified in interictal states. Therefore, interictal FDG-PET has greater sensitivity than interictal SPECT, especially in temporal lobe epilepsies (TLEs). Thus, 18F-FDG-PET is a necessary step in the presurgical evaluation of TLEs, but also of extratemporal epilepsies (ETEs), contributing to > 30% of the decision to undertake surgery. In addition, FDG-PET has particular diagnostic value in focal epilepsies showing normal magnetic resonance imaging (MRI). PET also has good prognostic value for post-surgical outcomes as well as cognitive impairment, especially in cases where the hypometabolism extent is limited. Moreover, the notion of an epileptic network is well highlighted by functional PET imaging, allowing better understanding of the pathological substrates of these disorders. Future development of quantitative analysis software and of novel radiotracers and cameras will certainly enhance its clinical usefulness.