Mass mortalities in bivalve populations have long been of particular concern, especially when the species supports a commercial fishery or is of conservation interest. Here we consider the evidence of mass mortalities of the edible cockle, Cerastoderma edule (L.). Through the construction of a conceptual model eight potential factors (or groups of factors) which may cause mass mortalities are identified and reviewed. These include: food limitation; density; oxygen depletion and organic loadings; temperature and salinity; parasites, pathogens and commensals; toxicants and other persistent pollutants; predation, and changes in sediment, suspended solids, topography and bathymetry. The interplay between factors in recognized and discussed based on evidence mainly from the published literature relating to temperate edible cockle beds. Anecdotal evidence is also reported from a structured survey of site-specific evidence provided by fisheries managers in England and Wales. Case studies from the UK and Europe indicate that there is often no single, clear generic cause of mass mortalities in cockle populations. The importance of linked site-specific scientific investigations and laboratory-based experiments to fill the gaps in our current understanding of mass mortalities in bivalve species is highlighted as necessary to take account of both local extrinsic and intrinsic factors.