Antibiotics have long been suspected of contributing to male infertility; however, there are remarkably limited data to support this premise. A major challenge for evaluating antibiotic effects is that the diseases they treat often have negative impacts on male reproduction, so treatment with the antimicrobial can improve reproductive endpoints. This is particularly true for diseases of the male reproductive tract. As a class, anti-parasitic drugs are toxic to eukaryotic cells and have significant potential for reproductive toxicity. A variety of these medications are also used in companion and food animal species; in this chapter we review the literature on anti-parasitic drugs on male reproduction in these species. In humans, only niridazole has been shown to cause reversible spermatogenic arrest in 20 men with schistosomiasis. Of the antifungal medications, ketoconazole has been shown in some studies to transiently decrease testosterone levels in men, but work is lacking for semen quality or fertility. We review studies of antibacterial medications in the chapter, with some minimal human data available for decreased semen quality in men taking nitrofurantoin, ciprofloxacin, ofloxacin, or sulfamethoxazole. These and some other antibacterials have been studied in other species with results suggestive of negative impacts on male fertility endpoints. In light of the common assumption of reproductive toxicity for antimicrobial medications, and the decided lack of supporting evidence, there is a substantial need for well-designed clinical trials in this area.