Human papillomavirus (HPV) infection is a necessary cause of cervical cancer; HPV testing capitalizes on this fact to maximize the clinical benefits of cervical screening and abnormal Papanicolaou (Pap) test management. HPV tests in combination with Pap tests are 96% to 100% sensitive for detection of cervical intraepithelial neoplasia (CIN) 2/3 and cancer. However, because HPV infection is common in young women and most commonly transient, HPV testing is not recommended as part of primary cervical screening for women younger than 30 years of age. HPV testing is recommended for women of any age for the clarification of atypical cells of undetermined significance (ASC-US) and as an option for follow-up of women with HPV-positive ASC-US, atypical squamous cells "cannot rule out high-grade," or low-grade squamous intraepithelial lesions not found to have CIN 2/3. HPV testing is also recommended as an alternative to colposcopy and/or cytology for follow-up of treated cases. Proper use of HPV testing improves the management of women with cytologic abnormalities. In addition, a negative HPV test in combination with a normal Pap test result in women age 30 and older allows the safe extension of the interval between cervical screenings. Thus, when used properly, HPV testing may reduce morbidity and mortality and do so in a cost-effective manner.