Background: Human papillomavirus (HPV), the virus responsible for cervical cancer, is the most common viral sexually transmitted infection in the United States. A vaccine was approved in 2006 that is effective in preventing the types of HPV responsible for 70% of cervical cancers and 90% of genital warts. Proposals for routine and mandatory HPV vaccination of girls have become sources of controversy for parents of school-aged youth, legislators, members of the medical community, and the public at large. Methods: The purpose of this article was to articulate the arguments used by advocates who either oppose or endorse routine, mandatory administration of the vaccine to school-aged girls, thereby assisting school health personnel in being effective participants in framing the relevant issues. Results: Controversy is grounded in moral, religious, political, economic, and sociocultural arguments including whether concerns that the vaccine increases sexual risk taking, sends mixed messages about abstaining from sexual intercourse, usurps parental authority, and increases the potential for development of new health disparities are offset by the value of administering a cost-effective, age-appropriate public health measure targeting a life-threatening problem. Conclusions: Careful consideration of the medical evidence and public health implications is critical but understanding the context of the debate is no less important to the task of responding to public concerns. School health personnel have a role in the discussion about HPV immunization. Being able to articulate the arguments presented herein can help authorities' responsiveness to parents and community groups as the dialogue about this particular health issue evolves further.