Recent neuroanatomical studies, neurochemical coding and physiological findings of multiple cotransmitter actions and/or receptor patterns, and the characterization of synaptic molecules and nitrergic (NOergic) signaling mechanisms may help for a better understanding of target-organ control in the autonomic nervous system. Thus, nitric oxide (NO) synthase, which generates the freely diffusible and short-lived messenger NO and expression of neurotrophic proteins (e.g., neurotrophins, glial cell-line-derived neurotrophic factor, fibroblast growth factors) in autonomic neural pathways or target organs suggest unique actions in autonomic neurotransmission. In central NOergic pathways, NO may serve as spatial (volume) messenger within hierarchically ordered autonomic neuron pools and convergent/divergent pathways for synchronized autonomic outflow. Likewise, NO modulates intraganglionic and interaxonal transmission and postganglionic activity including long-term potentiation. In the visceral targets, NO appears to be a spatial modulator in local intrinsic networks or at varicose terminals. In endocrine glands, NO possibly acts as synaptic coactivator or inhibitor, as a cotransmitter affecting stimulus-coupled exocytosis, or as a local vasoactive signal. The short-term neural messenger NO may also induce diffusible target-derived long-term neurotrophic signals, thereby supporting neuroeffector maintenance and plasticity, if not synaptic efficacy, in autonomic target-organ control.