Bivalve aquaculture accounts for 14%–16% of the average per capita animal protein of 1.5 billion people, supporting more than 200,000 livelihoods, mostly in developing countries. Massive mortality outbreaks of various cultured bivalves have been reported worldwide. Repeated episodes of mass mortality not only reduce the production and cause high economic losses but also have a negative impact on natural bivalve populations. The present article reviews the scientific evidence of mass mortality outbreaks of marine bivalve molluscs affected by extrinsic factors. It attempts to summarize the pertinent data published on specific research issues to improve understanding of the diverse factors. This helps to clarify the present state of research and to identify topics for future studies on bivalve mass mortality. It can be seen from the published data that bivalve mass mortality episodes are rarely caused by single factors but are more likely to be triggered by synergistic effects of two or more factors. Understanding these factors could aid in the development of good aquaculture practices and effective fishery management plans for bivalves.