The vago-vagal reflexes mediate a wide range of digestive functions such as motility, secretion, and feeding behavior. Previous articles in this series have discussed the organization and functions of this important neural pathway. The focus of this review will be on some of the events responsible for the adaptive changes of the vagus and the enteric neutral circuitry that occur after vagal injury. The extraordinary plasticity of the neural systems to regain functions when challenged with neural injury will be discussed. In general, neuropeptides and transmitter-related enzymes in the vagal sensory neurons are downregulated after vagal injury to protect against further injury. Conversely, molecules previously absent or present at low levels begin to appear or are upregulated and are available to participate in the survival-regeneration process. Neurotrophins and other related proteins made at the site of the lesion and then retrogradely transported to the soma may play an important role in the regulation of neuropeptide phenotype expression and axonal growth. Vagal injury also triggers adaptive changes within the enteric nervous system to minimize the loss of gastrointestinal functions resulting from the interruption of the vago-vagal pathways. These may include rearrangement of the enteric neural circuitry, changes in the electrophysiological properties of sensory receptors in the intramural neural networks, an increase in receptor numbers, and changes in the affinity states of receptors on enteric neurons.