The Mediterranean mussel Mytilus galloprovincialis is an ecologically and economically important species. It has been used in programs of monitoring of pollution, since it is sessile organism that is capable of accumulating pollutants in tissues through filter feeding. Due to an increase of pollutants in the environment, marine mussels present physiological alterations that compromise their innate immune system, which can latter lead to opportunistic diseases. The haemocytes are the cells in charge of the immune response in the Mediterranean mussel and in other mollusks. In this review, we summarize the physiological and genetic response capacity of these immune cells to the presence of xenobiotics, pathogens and the interplay. The identification of the basic mechanisms of immunity and their modulation in mussels can give important information for the possible utilization of this species as an invertebrate model for studies on innate immunity, future immunotoxicological studies, and predict changes in the community for the future.