In epilepsy, nuclear neuroimaging is an established modality in clinical practice to identify interictal hypometabolic or ictal hyperperfusion areas around the epileptogenic foci. Specific molecular imaging has also been used for scientific and clinical purposes beyond detecting changes in glucose metabolism and locating seizure foci. In this chapter, we first review past studies of the epileptic brain that have used advanced nuclear imaging with various neurotransmitter ligands, including ligands for γ-aminobutyric acid (GABA) and glutamate receptors and monoamines, as well as nuclear imaging tools to evaluate neuroinflammation and blood–brain barrier (BBB) integrity; then, we focus on a methodology for opioid receptor imaging in epilepsy.