Four families of trematodes were observed in histological sections during a 1992–1997 investigation of the parasites of zebra mussels Dreissena polymorpha. These included Aspidogastridae, i.e., Aspidogaster, Echinostomatidae, Bucephalidae, i.e., Bucephalus polymorphus, and Gorgoderidae, i.e., Phyllodistomum folium. This article describes the precise location of these trematodes in the tissues of D. polymorpha, provides graphic evidence of their effect on the organs they inhabit, and highlights the distinguishing morphological characteristics. Evidence of defense reaction of host to trematode infection, i.e., encapsulation of Aspidogaster and nacrezation of B. polymorphus, is also presented and is the first such report for zebra mussels. The histological photomicrographs included represent the first comprehensive series published on trematode infection of zebra mussels. These images, in conjunction with the morphological descriptions presented, should assist researchers in identifying the 4 major trematode taxa that they are likely to encounter in the tissue sections of zebra mussels.