Publisher Summary This chapter focuses on the structural considerations and subtype diversity of nicotinic receptors. Nicotinic receptors assemble as pentamers of individual subunits. Assembly occurs in a precise manner and order such that the assembled subunits encircle an internal membrane pore and the extracellular vestibule leading to the pore. Each subunit encodes a protein with four transmembrane spans. A relatively large cytoplasmic loop is found between transmembrane spans 3 and 4 with a short carboxyl terminus winding up on the extracellular side. All of the nicotinic receptors that are well characterized, to date, are cationic channels resulting in depolarization after activation. Typically postsynaptic nicotinic receptors, such as those found in ganglia and the neuromuscular junction, function through the simultaneous occupation of the receptor by more than a single agonist molecule. Agonist association and the ensuing channel opening reveals positive cooperativity in ligand binding. Nicotinic receptors are widely distributed in the central and peripheral nervous systems. In innervated skeletal muscle they are found in very high density localized to the motor end plate.