The male reproductive tract harbours effective immune mechanisms to protect the host from invading microorganisms. As the frontline of defence, the innate immune system has evolved receptors that recognise molecular patterns of pathogens to sense infections. These Toll-like receptors discriminate between different pathogen-associated molecules and activate signalling cascades that lead to immune responses, but can also result in tissue destruction leading to fertility disturbances. The testis is unique as it produces a large number of immunogenic cells expressing neo-antigens with no apparent adverse consequences for the majority of men. On the other hand the male gonad appears to be particularly susceptible to tissue damage resulting from infection or inflammatory reactions, a challenge that provides an important task both to clinicians and basic scientists. This review is intended to provide an overview of pathogens relevant in male reproductive tract infection, with a special emphasis on the testis. It also highlights the recent work broadening our understanding of the mechanisms underpinning germ cell loss in the presence of bacteria.