Publisher Summary Nicotinic cholinoceptor (nAChR) function in the brain tissue has been approached from a number of directions. Electrophysiologists have tended to concern themselves with the actions of exogenously applied acetylcholine (ACh) and nicotinic agents on single unit responses. Others have described the effects of nicotinic agents on neurotransmitter release, cerebral glucose utilization, cerebral blood flow and on behavior, principally in an attempt to understand the sites and actions of nicotine as a drug abuse. In contrast, very few researchers have investigated what might be assumed to be the primary function of brain nAChRs— that is, to mediate actions of ACh released from cholinergic nerves. The purpose of this chapter is therefore to highlight the evidence for nicotinic cholinergic transmission in mammalian brain. From this chapter it is clear that nAChRs are widely distributed in the brain. There is an abundance of evidence that neurons in many sites in the brain express nAChRs and can be activated by exogenous ACh and nicotinic agonists. There is also a rich literature describing the anatomical organization of CNS cholinergic neurons. In contrast, there are very few documented examples of nicotinic cholinergic transmission in the brain. In most cases, the crucial experiments remain to be carried out.