The cough reflex as part of an integrated protective mechanism for adequate bronchoelimination is vital in maintaining the integrity of the pulmonary parenchyma. While it is undoubtedly true that more patients have died from an inability to cough effectively than from the act of coughing itself, adequate control of useless cough is often necessary in order to preserve the health and wellȁbeing of the patient. Until recently, cough mixtures were compounded empirically and assessed clinically on the basis of subjective response. Based upon physiologic and pharmacologic studies on the mechanics and regulation of the cough reflex together with the development of new techniques for eliciting a reproducible cough with graded stimuli in animals and man, quantitative objective studies of antitussive activity are now possible. This has stimulated the search for new compounds devoid of the analgesic and narcotic properties of the opium derivatives. Some of the new synthetic compounds discussed in this review have demonstrated antitussive activity equivalent to that of codeine and are replacing the older narcotic preparations in the symptomatic management of cough.