Cough is a very common clinical symptom and current therapies are largely ineffective, indicating a major unmet medial need. There is a pressing need to develop novel and safe antitussive therapies. This is likely to arise from better understanding of the sensory nerves involved in cough and the signalling pathways that are activated. A major therapeutic target should be sensitization of the cough reflex which is a feature of patients with both acute (virally induced) cough and chronic cough, including chronic idiopathic cough. Studies on human cough mechanisms are limited. There are several novel therapeutic approaches that are currently being explored. Perhaps the most promising drugs are transient receptor potential vanilloid-1 (TRPV(1)) antagonists, selective cannabinoid agonists (CB2 agonists), maxi-K channel openers and P2X3 antagonists. New cough therapies may target airway nerve sensitization and may best be delivered as inhalers to minimize any systemic effects. Understanding the intercellular signalling pathways involved in nociception may lead to novel drugs, such as p38 mitogen-activated protein (MAP) kinase inhibitors, being used in the treatment of cough in the future. It is also likely that several novel treatments that are developed as analgesics will also prove to be beneficial in the treatment of cough.