Abstract There is growing experience that supports the use of vagus nerve stimulator (VNS) therapy as an effective treatment for complex epilepsy. The number of clinical conditions for which VNS has been tried and reported anecdotally to help continues to grow. As such, VNS represents the most widely clinically utilized form of neuromodulation therapy in clinical practice today. This chapter reviews the evolution of understanding of the rationale for VNS, summarizes outcomes and indications reported to date, and discusses surgical considerations in the surgical placement of a VNS device.