Nicotinic acetylcholine receptors (nAChRs) warrant attention, as they play many critical roles in brain and body function and have been implicated in a number of neurological and psychiatric disorders, including nicotine dependence. nAChRs are composed as diverse subtypes containing specific combinations of genetically-distinct subunits and that have different functional properties, distributions, and pharmacological profiles. There had been confidence that the rules that define ranges of assembly partners for specific subunits were well-established, especially for the more prominent nAChR subtypes. However, we review here some newer findings indicating that nAChRs having largely the same, major subunits exist as isoforms with unexpectedly different properties. Moreover, we also summarize our own studies indicating that novel nAChR subtypes exist and/or have distributions not heretofore described. Importantly, the nAChRs that exist as new isoforms or subtypes or have interesting distributions require alteration in thinking about their roles in health and disease.