Background: Anorectal and pharyngeal infections with Chlamydia trachomatis (CT) and Neisseria gonorrheae (NG) are commonly observed in men who have sex with men (MSM). There is increasing evidence that such infections at extragenital sites are also common in women. In both sexes, these infections are largely overlooked as they are not routinely tested for in regular care. Testing based on sexual behavior or symptoms would only detect half of these extra-genital infections. This paper elucidates the differences and similarities between women and MSM, regarding the epidemiology of extra-genital CT and NG. It discusses the clinical and public health impact of untested extra-genital infections, how this may impact management strategies, and thereby identifies key research areas. Discussion: Extra-genital CT is as common in women as it is in MSM; NG in women is as common at their extragenital sites as it is at their genital sites. The substantial numbers of extra-genital CT and NG being missed in women and MSM indicate a need to test and treat more patients and perhaps different choices in treatment and partner management strategies. Doing so will likely contribute to reduced morbidity and transmission in both sexes. However, in our opinion, it is clear that there are several knowledge gaps in understanding the clinical and public health impact of extra-genital CT and NG. Key research areas that need to be addressed concern associated morbidity (anorectal and reproductive morbidity due to extra-genital infections), 'the best' management strategies, including testing and treatment for extra-genital CT, extra-genital treatment resistance, transmission probabilities between partners and between anatomic sites in a woman, and impact on transmission of other infections. Data are also lacking on cost-effectiveness of pharyngeal testing, and of NG testing and anorectal CT testing in women. Gaps in the management of extra-genital CT and NG may also apply for other STIs, such Mycoplasma genitalium. Summary: Current management strategies, including testing, to address extra-genital CT and NG in both sexes are suboptimal. Comparative data on several identified key themes in women and MSM are lacking and urgently needed to guide better management of extra-genital infections.