Persistent high-risk human papillomavirus (HPV) infection is a necessary precursor for the development of cervical cancer. Recent data demonstrating the sensitivity of HPV testing has led to consensus group updates of how to best screen women in the United States. The newest recommendations incorporate HPV testing for women 30 to 65 years of age, but do not yet recommend primary screening with HPV testing alone. With the advent of HPV vaccination and consequent shift in the prevalence of HPV-related disease, the role of cervical cytology as primary testing in national screening programs will be further called into question.