Neuromodulation is an increasingly utilized therapy for the treatment of people with drug-resistant epilepsy. To date, the most common and effective target has been the thalamus, which is known to play a key role in multiple forms of epilepsy. Neuroimaging has facilitated rapid developments in the understanding of functional targets, surgical and programming techniques, and the effects of thalamic stimulation. In this review, the role of neuroimaging in neuromodulation is explored. First, the structural and functional changes of the thalamus in common epilepsy syndromes are discussed as the rationale for neuromodulation of the thalamus. Next, methods for imaging different thalamic nuclei are presented, as well as rationale for the need of direct surgical targeting rather than reliance on traditional stereotactic coordinates. Lastly, we discuss the potential role of neuroimaging in assessing the effects of thalamic stimulation and as a potential biomarker for neuromodulation outcomes. •Structural and functional thalamic abnormalities are seen in various epilepsy types.•Nucleus-specific abnormalities underpin the rationale for neuromodulation targets.•Deep brain stimulation affects widespread network nodes that are abnormal in epilepsy.