spp. are a genus of bacteria for which two human-associated species exist: and Their definition as a pathogen in the context of nongonococcal urethritis (NGU) and infertility among males remains highly controversial, largely due to historically high rates of isolation of these bacteria from the urethra of seemingly healthy men. This review summarizes the emerging evidence suggesting a true pathogenic role of these bacteria under specific conditions, which we term risk factors. We examine the historical, clinical, and experimental studies which support a causal role for spp. in the development of NGU as well as some of the proposed mechanisms behind the association of spp. and the development of infertility. Finally, we discuss the potential for developing a case-by-case risk-based approach toward the management of men who present with seemingly idiopathic NGU but who are positive for spp.