This paper reviews important new evidence indicating that traumatic brain injury can produce more widespread derangements to the neuronal cytoskeleton than previously recognized. Although cytoskeletal derangements in axons have long been documented, recent data suggest that traumatic brain injury can produce structural derangements to dendrites and cell bodies as well. Many of these investigations have employed in vivo models to provide important insights into mechanisms possibly mediating the acute loss of cytoskeletal proteins, including disturbances in calcium homeostasis and activation of calcium-dependent proteolytic enzymes. However, we have little understanding of processes mediating the recovery of cytoskeletal proteins following injury. This paper provides recent evidence from in vitro models of central nervous system injury that neurotrophic proteins can enhance the recovery of the neuronal cytoskeleton. Neurotrophin-based therapy could employ either administration of exogenous neurotrophic proteins and/or transfection of cDNA for appropriate neurotrophins.