School nurses are at the forefront of health care providers for many families of junior high and high school students and are used as primary sources of information and guidance about recommended student vaccinations. In the case of the relatively new vaccine for human papillomavirus (HPV), school nurses must be both knowledgeable about the infection itself and unbiased when asked to give students and families information about the vaccine. This article explores the development and current status of HPV and the HPV vaccine and the ethical principles of autonomy, utilitarianism, beneficence, nonmaleficence, justice, and cultural and religious issues as they relate to discussions with students and families about HPV vaccinations. School nurses are advocates for the health of students. Therefore, they must critically evaluate the application of these ethical principles when providing information and recommendations about the HPV vaccination.