Abstract Recent clinical studies have emphasized the up-regulation (sensitization) of cough in pathological conditions of the airways. However there are also many situations where voluntary and reflex cough can be down-regulated. These include: (1) chemical stimulation of breathing by hypercapnia or hypoxia or both, establishing that cough sensitivity can be inversely related to drive to breathing; (2) voluntary inhibition of cough, probably similar in mechanism to the depression of cough that can be induced by hypnosis and other branches of alternative medicine; (3) the placebo effect of many antitussive treatments; (4) sleep; (5) general anaesthesia; (6) central nervous disorders such as coma, stroke, Parkinson's disease and several other conditions where the defect in the protective reflexes may lead to aspiration pneumonia; (7) increased activity in various afferent inputs from viscera in the thorax and abdomen; (8) a number of bronchopulmonary clinical disorders. The list is long, but regrettably the nervous mechanisms of these down-regulations have been little studied. In addition there are a number of situations, such as exercise, coitus, talking and singing which, while important to coughing humans, have been not investigated in relation to cough. Most of the studies have been with experimental animals, and their extension to human research is desirable. In view of the importance of cough and other defensive reflexes in maintaining human well-being, far more research is needed. The field is wide-open.