Since the cloning and expression of many of the G protein-coupled receptors during the 1980s, there has been a massive increase in our understanding of many aspects of their function. The use of molecular biology to engineer and express mutant receptors has made it possible to determine key amino acids involved in receptor function. Although advances in molecular biology have contributed greatly to our understanding of the pharmacology and structure of the five subtypes of muscarinic receptor, much remains to be learned about the factors that regulate their expression and function. This review by El-Bdaoui Haddad and Jonathan Rousell describes the current state of awareness and highlights recent advances made in the elucidation of the mechanisms involved in muscarinic receptor regulation. Because most is known about the regulation of expression of the M2 receptor subtype, particular attention will be paid to it. Furthermore, this receptor subtype plays an important role in regulating acetylcholine output from airway cholinergic nerves, and there is substantial evidence from studies both in vivo and in vitro in human and animal models that these receptors are dysfunctional in asthma.