During development, neurotrophic factors are known to play important roles in regulating the survival of neurons in the autonomic nervous system (ANS) and the formation of their synaptic connectivity with their peripheral targets in the cardiovascular, digestive, and other organ systems. Emerging findings suggest that neurotrophic factors may also affect the functionality of the ANS during adult life and may, in part, mediate the effects of environmental factors such as exercise and dietary energy intake on ANS neurons and target cells. In this article, we describe the evidence that ANS neurons express receptors for multiple neurotrophic factors, and data suggesting that activation of those receptors can modify plasticity in the ANS. Neurotrophic factors that may regulate ANS function include brain-derived neurotrophic factor, nerve growth factor, insulin-like growth factors, and ciliary neurotrophic factor. The possibility that perturbed neurotrophic factor signaling is involved in the pathogenesis of ANS dysfunction in some neurological disorders is considered, together with implications for neurotrophic factor-based therapeutic interventions.