Genetic studies in the model organism Caenorhabditis elegans have made valuable contributions to continuing advances in our understanding of cholinergic synapse biology and cholinergic transmission. C. elegans possesses a large and diverse family of nicotinic acetylcholine receptor (nAChR) subunits that share significant sequence similarity with vertebrate nAChR subunits. As is the case for vertebrates, C. elegans nAChR subtypes mediate excitatory synaptic responses to ACh release at the neuromuscular junction and are also widely expressed in the nervous system. Detailed knowledge of C. elegans neural connectivity patterns (wiring diagram), coupled with the ease of genetic manipulations in this system, enables high-resolution investigations into functional roles for specific receptor subtypes in the context of anatomically defined circuits. In this chapter, we review methods for the analysis of C. elegans nAChRs with an emphasis on strategies for identifying and characterizing genes involved in their biological regulation in the nervous system. These methods can be easily adapted to the study of other organisms as well as other receptor classes.