Apoptosis plays a major role in many biological processes which require or result in reduction of cell numbers. In the nervous system, apoptosis has been identified as a key mechanism regulating growth and development as well as the response to injury and tissue repair. The tethered cord syndrome (TCS) arises from fixation of the caudal end of the spinal cord resulting from several different etiologies. Distal fixation of the cord produces stretching and development of shear forces within cord tissue and has been associated with various metabolic and electrophysiological derangements. Previous studies have focused on ischemia as the pathophysiological basis of the neurological deficits that occur in this syndrome. However, more recent evidence suggests that apoptosis may be a key determinant of the extent of spinal cord injury and degree of neurological deficit following mechanical injury. The molecular biology of apoptosis is becoming increasingly well characterized, and several studies have addressed its role in spinal cord injury. Neuronal and oligodendrocyte populations within spinal cord tissue are known to be sensitive to ischemia and oxidative stress, but also readily undergo apoptotic cell death in response to various stimuli. It is likely that ischemia and apoptosis are interrelated processes that both contribute significantly to the histopathological features and functional loss seen in tethered cord syndrome.