Mesial temporal lobe epilepsy (MTLE) is presumed to develop progressively as a consequence of synaptic reorganization and neuronal loss, although the exact etiology of seizure development is unknown. Nearly 30% of patients with MTLE have disabling seizures despite pharmacological treatment, and the majority of these patients are recommended for resection. The authors review cell transplantation as an alternative approach to the treatment of epilepsy. Recent work in animal models shows that grafted neuronal precursors that differentiate into inhibitory interneurons can increase the level of local inhibition. Grafts of these inhibitory neurons could help restore equilibrium in MTLE. Developing a sound transplantation strategy involves careful consideration of the etiology of MTLE and the expected functional role of transplanted cells. These issues are reviewed, with a focus on those factors most likely to influence clinically applicable results.