Several tools are available to map brain electrical activity. Clinical applications focus on epileptic activity, although electric source imaging (ESI) and electroencephalography-coupled functional magnetic resonance imaging (EEG–fMRI) are also used to investigate non-epileptic processes in healthy subjects. While positron-emission tomography (PET) reflects glucose metabolism, strongly linked with synaptic activity, and single-photon-emission computed tomography (SPECT) reflects blood flow, fMRI (BOLD) signals have a hemodynamic component that is a surrogate signal of neuronal (synaptic) activity. The exact interpretation of BOLD signals is not completely understood; even in unifocal epilepsy, more than one region of positive or negative BOLD is often observed. Co-registration of medical images is essential to answer clinical questions, particularly for presurgical epilepsy evaluations. Multimodal imaging can yield information about epileptic foci and underlying networks. Co-registering MRI, PET, SPECT, fMRI, and ESI (or magnetic source imaging) provides information to estimate the epileptogenic zone and can help optimize surgical results.