Nicotinic acetylcholine receptors (nAChRs) play an important role in various processes involved in regulating systemic blood pressure. These receptors are expressed at excitatory cholinergic synapses between sympathetic preganglionic neurons and postganglionic sympathetic neurons and link the integrative activities of the CNS with peripheral effector mechanisms of the sympathetic nervous system. Nicotinic AChRs are also expressed on a subset of vagal afferent neurons, including those involved in baroreceptor reflexes. This review discusses the developmental expression of nAChRs on vagal afferent neurons and two factors that influence the differentiation of these neurons: ganglionic satellite cells and neurotrophins. In addition, this review discusses two important properties of neuronal nAChRs: inward rectification and calcium permeability. At the molecular level, intracellular polyamines, acting as gating particles, effectively block the receptor pore in a voltage-dependent manner, producing inward rectification. Moreover, a critical structural determinant underlies both the block by intracellular polyamines and calcium permeability. Finally, this review discusses the modulation and block of neuronal nAChRs by extracellular polyamines and the possible implications for neurodegenerative diseases.