The male reproductive system (MRS) is a complex system, considering its isolated anatomical locations and special microenvironments. The major organs of the MRS, including the testis, epididymis, seminal vesicle, and prostate, are relatively separated and have distinct immune status for protecting male germ cells from adverse immune responses and counteracting microbial infection for conducting their functions. A large spectrum of viruses has tropism for the MRS and may impair male fertility. To defend against invading viruses, the MRS has developed a local innate antiviral environment to reduce virus-impaired male fertility. All major tissue cells are well equipped with innate antiviral machinery. Both tissue-specific cells and immune cells are involved in the antiviral defense against viral infection of the MRS. Understanding the mechanisms underlying local innate antiviral responses in the MRS can aid in the development of preventive and therapeutic strategies for viral diseases. This chapter focuses on pattern recognition receptor-mediated innate antiviral responses in the major cells of the testis, epididymis, seminal vesicle, and prostate.