Cough is an important defensive reflex of the upper airway and is also a very common symptom of respiratory disease. Cough following an upper respiratory viral infection is transient, and persistent cough is associated with a whole range of conditions, such as asthma, rhino-sinusitis and gastro-oesophageal reflux. Treatment directed at these conditions may improve the associated cough. There is often a need, however, to control cough itself whatever the cause. The most effective drugs in this class are the opioids, such as morphine, codeine or pholcodeine, but at effective doses they have side effects including drowsiness, nausea, constipation and physical dependence. Investigations into the cough reflex and into the potential mechanisms of sensitised cough reflex have uncovered several potential targets for novel drugs. New opioids apart from mu-agonists such as kappa- and delta -receptor agonists, have been developed, in addition to non-opioids such as nociceptin. Neurokinin receptor antagonists, bradykinin receptor antagonists, vanniloid receptor VR-1 antagonists may be beneficial by blocking effects of tachykinins and sensory nerve activation. Local anaesthetics, blockers of sodium-dependent channels and maxi-K Ca2+-dependent channel activators of afferent nerves are inhibitors of the cough reflex. Some of these novel agents may act centrally or peripherally or at both sites as antitussives. Large scale trials of these novel compounds have not been carried out in cough in man but there is a serious need for more effective antitussives devoid of side effects.