The application of functional magnetic resonance imaging (fMRI) to elucidation of seizures and epilepsy has been built primarily upon a framework derived from cortical responses to periodic sensory (and cognitive) stimuli. This analytical approach relies upon assumptions that may be less applicable to the problem of seizure origination. Because of the heterogeneous and complex nature of seizures, a number of quantitative methodologies have been derived to understand fMRI changes that are associated with epileptiform neural activity. Separated broadly, these can be divided into those making some set of assumptions about the form of the MRI signal response to neural activation (the general linear model), and those that are data driven. It is likely that a combination of methodologies, where data driven methods are "informed" by knowledge of the underlying neurobiological process will provide the greatest insight into the underlying neurobiological basis of seizure origination.