For the American Cancer Society (ACS), the time for primary human papillomavirus (HPV) screening implementation has unequivocally arrived for the United States, but it will require broad knowledge mobilization and addressing logistical barriers to engage the public and health providers. The ACS is using its convener role and marshalling its considerable educational and knowledge dissemination resources to advance primary HPV screening in the United States and to share best practices from countries that have done the same through the ACS Primary HPV Screening Initiative.