Control strategies and routine biomonitoring programs arc commonly performed worldwide using sentinel marine invertebrates, such as mussels of the genus Mytilus, for assessing the "health status" of the aquatic environment. Those species can accumulate and tolerate xenobiotics at levels higher than those being present into the aquatic environment, thus providing accurate and reliable biological endpoints (e.g. physiological, behavioral, cellular, biochemical and molecular indices) that can be measured in their tissues. Taking under consideration the significance of bivalves for assessing the environmental hazard of xenobiotics being present into the water medium, as well as the key role of digestive gland as a target-tissue for the compounds ingested in the organism, the present study aimed to summarize available data on the effects of different categories of xenobiotic compounds, previously characterized as a potential threat for the marine ecosystems. In this context, different types of pharmaceuticals and personal care products (PPCPs), biocides, microplastics (MPs) and nanoparticles (NPs), currently investigated in mussels' digestive gland, using a battery of experimental approaches and analytical methods, as well as stress indices evaluation, are briefly described and further discussed in order to elucidate not only the presence and the toxic mode of action of xenobiotics, but also the important role of the digestive gland as a reliable target-tissue for investigating the effects of xenobiotics at cellular, biochemical, and molecular levels. (C) 2018 Elsevier B.V. All rights reserved.