Electrical stimulation of cranial and peripheral nerves has been used to ameliorate a variety of neurologic disease states and neural injuries over the past 20 years. In this review, clinical applications and the histopathologic results of chronic implants in animals and humans are discussed, and the results of neural damage models developed at Huntington Medical Research Institutes are summarized. Chronically implanted electrode arrays may produce neural injury by either mechanical factors or by continuous, high-frequency electrical stimulation. The margin of safety to avoid electrically induced injury may be increased by minimizing the frequency or total stimulation time, and by the use of an intermittent duty cycle. The protocols presently being used for the stimulation of the vagus nerve to effect inhibition of seizures appear to have an adequate margin of safety.