This chapter describes the role of human papilloma virus (HPV), fundamentals about the Papanicolaou (Pap) smear, and the prevention of cervical cancer. The conventional Pap smear has been one of the most effective screening tests for cervical cancer prevention. Cervical cytological testing has been successful in preventing cervical cancer in women who present for screening with reductions of the cervical cancer rate by 70% in the last 100 years. Pap test screening should be initiated at the onset of sexual activity, within three years of onset of sexual activity, or at age 21. Prevention of diseases that come from infection with high risk HPV, such as precancerous cervical lesions, genital warts, vaginal and vulvar lesions, and cervical cancer is now possible by vaccination (Gardasil) against HPV types 6, 11, 15 and 18. With the use of the HPV vaccine, HPV infection is reduced and cervical cancer may be mostly prevented.