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Multixenobiotic defence mechanism (MXDM) consists in a cellular system that functions as membrane extrusion pumps effluxing organic compounds out of the cells. In bivalves, it represents a primordial protection against toxic effects of organic xenobiotics in preventing their cellular accumulation. It has raised attention during the last decade for its potential to be used as a biomarker of pollution. This article reviews the fundamental knowledge on the MXDM system in bivalves and the methods proposed to assess its activity. Finally, it reviews the major results of laboratory and field studies that enabled to hypothesise that MXDM could be used as a biomarker of environmental stress rather than of pollutant exposure.