The unkeratinized epithelium of the inner human foreskin is thought to be more susceptible to human papillomavirus (HPV) entry than the rest of the penis. However, studies exploring a potential association between male circumcision and HPV infection have produced conflicting results. The present review stratifies the evidence based on methods of sampling and detection of HPV infection, HPV type, and the stage of infection. This approach reveals that circumcision reduces the risk of HPV infection in a stage- and type-specific manner. There is no consistent association of HPV acquisition with circumcision status, indicating that circumcised men may be no more protected from initial HPV infection than their uncircumcised peers. Circumcision is not protective against nononcogenic types of HPV, but is associated with a reduced prevalence and persistence of oncogenic HPV infections. Circumcised men are also less susceptible to multiple infections. These findings indicate that circumcision modulates HPV persistence rather than acquisition. Through promoting HPV infection clearance, male circumcision could be an important adjunct to education, condom use, and vaccination in reducing the global burden of HPV morbidity and mortality.