There have been considerable advances in antiepileptic drug (AED) therapy in recent years. More recently, a series of revolutionary technologies combining optics or organic compounds with genetics have been used to suppress seizures on demand. These results suggest new treatment approaches and provide a good basis from which future clinical studies might be developed. This chapter considers the principles behind novel focal treatment strategies, critically reviews the work to date and discusses the potential for translation of these advances into new treatment options for patients with currently intractable disease. Neuronal grafting holds the promise of effecting potentially permanent local change and initial studies demonstrate the feasibility of restoring neuronal loss, altering circuitry or increasing local neurochemical concentrations. Viral vectors are important tools for gene therapy of terminally differentiated cells. Focal treatment techniques in epilepsy offer a novel approach to help more patients lead seizure-free lives in the years to come.