It is astonishing that a scientific article specifically discussing antitussive therapeutics written in 1958, the year the US Food and Drug Administration approved dextromethorphan, would be reasonably up to date if published today. In essence, for the past 40 years, physicians wishing to quell the unproductive and chronic cough that persists beyond treatment of any underlying disorder have leaned heavily on the use of codeine (and related opioids), and dextromethorphan. Not only is the efficacy of these products questioned, poison control centers reported > 750,000 calls relating to these drugs from 2000 to 2008, raising concerns about their safety, especially in the pediatric population.1-3 Codeine, dextromethorphan, and other opiate derivatives act centrally to inhibit cough. In recent years new information about the regulation of the peripheral neural pathways leading to cough have emerged, leading to optimism that novel, safe, and effective antitussive drugs may be developed that directly target the primary afferent (sensory) nerve. Such a drug, in theory, may be more effective than existing drugs and at the same time unhampered by central side effects. Information about these nerves and three examples of how they may be targeted are discussed herein.