Malignant peripheral nerve sheath tumors (MPNSTs) are a rare variety of soft tissue sarcoma of ectomesenchymal origin. MPNSTs arise from major or minor peripheral nerve branches or sheaths of peripheral nerve fibers and are derived from Schwann cells or pluripotent cells of neural crest origin. Arthur Purdy Stout played a pivotal role in the development of our current understanding of the pathogenesis of peripheral nerve sheath tumors by identifying the Schwann cell as the major contributor to the formation of benign and malignant neoplasms of the nerve sheath. Although this fact remains essentially true, the cell of origin of the MPNST remains elusive and has not yet conclusively been identified. Some have suggested these tumors may have multiple cell line origins. In the present review, MPNSTs and their epidemiology, diagnosis, management, and treatment are discussed.