Overt signs of toxicity (loss of appetite, loss of equilibrium, discoloration, or death) are nearly always preceded by biochemical, physiological, and/or morphological changes in the organism. The ability to qualitatively or quantitatively measure these changes prior to death of the organism can often provide early indications of toxicity and valuable insights into the mechanisms of toxicity. This chapter concerns the field of histopathology and its importance, use, and application in aquatic toxicology. Histopathology is the study of the structure of abnormal tissue. Examination of tissues from fish and other aquatic organisms after death may serve to identify the cause of death and possibly the causative agent. This information along with physiological and biochemical data may provide a more complete and accurate description of the activity of a chemical agent.