The cough reflex pathway is characterized by a remarkable plasticity often resulting in a persistent and uncontrollable urge to cough during airway inflammation. In many instances cough becomes up regulated to the extent that ceases to fulfill its defensive role in protecting the airways. The exact mechanisms underlying this plasticity are unknown and likely involves a variety of factors influencing the function of the peripheral and central nervous system. This review outlines the evidence of increased cough sensitivity during airway disease. This is followed by a discussion of the peripheral mechanisms involved including the potential role of inflammatory mediators, neutrophins and changes in the airway mucosal structure. A greater understanding of the mechanisms leading to enhanced cough should lead to the development of more effective therapeutic strategies.