Histopathology is acknowledged as the most sensitive endpoint for detecting testicular toxicity. However, identification and interpretation of chemically induced changes in the testis require fundamental knowledge of spermatogenesis, its dynamics and regulation. Changes in the rest of the reproductive tract are also frequently inter-related, being the result of or cause of disturbance in testicular spermatogenesis. This unit provides practical guidelines on how to evaluate testicular histopathology and how to utilize staging in a qualitative evaluation. It also provides an overview of the most common chemically induced lesions and their potential significance with respect to etiology and functional consequences.