Microbial infections and immunological disorders in the male reproductive system (MRS) are among the etiological factors of male infertility. The MRS, particularly the testis and epididymis, adapt special immune privileged environment to protect sperm from adverse immune response. However, microbial infections, chemical toxins, and physical trauma may disrupt the immune homeostasis in the MRS and induce local inflammation or autoimmune responses, thereby perturbing fertility. Inflammation in the MRS is characterized by leukocyte infiltration, increased levels of proinflammatory cytokines, and impairment of tissue function. Autoimmune responses to male germ cell antigens may lead to a chronic inflammation in the MRS and the generation of antisperm antibodies (ASAs) that impair sperm function. Understanding the mechanisms underlying infectious and immunological infertility can aid in the development of preventive and therapeutic approaches for the disease. This article describes major microbial infections and immunological disorders in the MRS, as well as their detrimental effects on male fertility.