In recent years, mussels have already become commercially important seafood species worldwide. Mussels accumulate a wide range of metals in their soft tissue. Thus, the determination of accumulated concentrations of heavy metals, such as Pb, Cd, Hg, and As, in mussels is essential because of their usage as seafood and the potential adverse effects of their consumption on human health. In this review, these issues are presented and discussed using the Mediterranean mussel as an example. is very efficient at converting low value victuals into high quality animal protein. The production of in Mediterranean countries has been increasing rapidly, but Spain is still the largest producer of mussels. Only China has a larger production of these mussels than Spain. is a filter feeding animal and accumulates a wide range of metals from their environment. The metal concentrations in the soft tissue of are indicators of marine ecosystems contamination. In the same time, the bioaccumulation of heavy metals remains an issue concerning the consumption of mussels. Thereby, the Cd, Pb, Hg, and As concentration measurement in mussel soft tissue as a seafood have become significant. A review of literature data revealed large variations in the Cd, Pb, Hg, and As concentrations in from their endemic areas, e.g., Mediterranean, Adriatic, and Black Sea, and the concentrations of these toxic metals were generally in the following order: As > Pb > Cd > Hg. The guidelines on heavy metals for seafood safety set by different countries and associations are reviewed. Comparison of the published data with European legislation showed that the levels of the heavy metals generally did not exceed the existing limits in all the mussels analyzed, excluding mussels from hot spots, such as lagoons and harbors, in the Mediterranean, Adriatic, and Black Sea.