Sex hormones influence susceptibility and disease predisposition for many genital tract infections. This review describes the mechanisms by which sex steroids affect mucosal immunity, with particular reference to human immunodeficiency virus (HIV) and genital herpes, and the stage-specific effects of hormonal contraception on human papillomavirus (HPV) infection. Estrogen's role is important in the early stages of several infections as it stimulates antibody- and cell-mediated immune responses. There is increased expression of some cytokines in peripheral blood and vaginal fluids during the follicular phase of the menstrual cycle and with use of hormonal contraception. Whether estrogen exerts a protective or deleterious influence depends on the infecting organism and stage of infection or disease. Estrogen apparently reduces susceptibility to primary HPV infection but in the event of persistent HPV infection, sex steroid hormones (estrogen and/or progesterone) are associated with progression to cervical cancer. It is important that these stage-specific effects are better described because most vaccines will try to prevent either infection or disease. Clinicians with patients at high risk of sexually transmitted infections, especially HIV, require better information on the risks associated with different hormonal contraceptive regimes.