Matrix metalloproteinases (MMPs) are a family of zinc and calcium-dependent endopeptidases that play a key role in extracellular matrix (ECM) degradation. MMPs are known to be important in normal remodelling processes. Overexpression and activation of MMPs or an imbalance of active MMPs and tissue inhibitors of metalloproteinases (TIMPs) has been linked with a number of specific disease states associated with the breakdown and remodelling of the extracellular matrix. MMPs and TIMPs play a role in the development and progression of conditions such as acute and chronic otitis media, nasal polyposis and Sjogren’s disease of salivary glands. Their role in allergic rhinitis has not been proven although they do appear to have a role in asthma, a condition closely linked to rhinitis. The use of a broad spectrum MMP inhibitor has been shown to alter the outcome of acute otitis media and otitis media with effusion. Therapeutic strategies with anti-MMP molecules are currently being developed and may play a role in modulating the course of non-neoplastic otorhinolaryngological disease in the future.