Traumatic spinal cord injury (SCI) results in devastating and often permanent disability for which no effective biologic therapies exist. The injury initiates a cascade of complex, interrelated pathologic processes leading not only to cell death at the injury site and in higher brain centers but also to the severing, demyelination and physiologic inactivation of axons and the generation of an environment hostile to neural repair. Numerous studies have increased our understanding of why regeneration fails following SCI and documented promising experimental interventions to overcome this failure. Advances in our knowledge of stem cell biology over the past decade have raised hopes that grafts with the potential to differentiate into subsets or all the major cells of the spinal cord will be able to replace neurons and glial cells that have been destroyed or rendered dysfunctional by injury. The isolation and characterization of stem cells and lineage-restricted precursors from multiple regions in the developing and adult central nervous system (CNS), as well as from tissue outside the nervous system, bring these expectations closer to reality (see Volume I, Chapter 18). In addition, the discovery of endogenous precursor cells in the adult spinal cord revealed another source of cells that may be amenable to therapies. These ideas have captured the imagination because, although we are only beginning to understand the promises and pitfalls of this approach, the need for effective treatments for SCI is urgent (see Volume II, Chapter 37).