Cervical ectopy, which occurs when the columnar epithelium of the endocervical canal extends outwards into the ectocervix, has been suggested to increase the susceptibility to HIV infection in at-risk women. This study summarizes observational studies, primarily conducted in sub-Saharan Africa, that have assessed a possible causative association between cervical ectopy and HIV acquisition and also examines the biological plausibility as well as other cofactors that may mediate this association. Only about half of the studies reviewed found cervical ectopy to be a significant risk factor for HIV acquisition. The reasons for these divergent results still remain to be fully elucidated. Understanding biological factors that affect HIV susceptibility provide opportunities to identify prevention strategies to reduce the risk of HIV acquisition.