The two principal features of airway goblet cells are rapid secretion of mucin onto the airway surface and increase in number (hyperplasia) with chronic inhaled 'insult'. The first is associated with homeostasis, the latter with pathophysiology. Myristoylated alanine-rich C kinase (MARCKS) is a key molecule regulating mucin exocytosis, a process also involving cooperative interaction between protein kinase (PK) C and PKG. The epidermal growth factor (EGF) cascade and calcium activated chloride channels (CLCA) are key signalling molecules involved in development of goblet cell hyperplasia, with Bcl-2, an inhibitor of apoptosis, involved in maintenance of hyperplasia. Goblet cell hyperplasia and associated mucus hypersecretion is a pathophysiological feature of asthma and chronic obstructive pulmonary disease (COPD). Novel therapeutic strategies to prevent or reverse goblet cell hyperplasia include inhibitors of EGF receptor tyrosine kinase and CLCA, of which viable pharmaceutical molecules are now available for clinical trial in hypersecretory conditions of the airways.