The production of melanin is a complex process involving biochemical cascades, such as the pro-phenoloxidase (proPO) system, and enzymes, such as phenoloxidases (POs). Different studies have shown a strong correlation between the decrease in PO activities and the occurrence of diseases in bivalve invertebrates, leading to mor-talities in the host. Results of these studies suggest that POs could play a fundamental role in defense mechanisms in bivalves. This article reviews the fundamental knowledge on the proPO system in bivalves and the methods used to assess PO activities. Finally, this is the first report on the major findings of laboratory and field studies that indicate that a type of PO in bivalves, the laccase enzyme, is inducible and involved in the 1) immune 2) antioxidant and 3) detoxification roles in bivalves, and might be an ecological potential biomarker of environmental stress.