Cervical cancer, caused by oncogenic types of human papillomavirus (HPV), remains a major health problem worldwide. The recent introduction of a quadrivalent vaccine (Gardasil(R)), which targets HPV strains responsible for approximately 70% of cervical cancer cases and 90% of genital warts, has ushered in new hope of substantially reducing global prevalence of HPV disease. A further bivalent HPV vaccine (Cervarix(TM)) is in the offing. However, many issues still need to be addressed, including actual vaccine efficacy in preventing cervical cancer, public acceptance, use of the vaccine in men, vaccine access, costs, and impact of the vaccine on cervical cancer screening programs. This review analyzes some of these issues, and emphasizes the need for a coordinated effort of patients, parents, health professionals, hospitals, and policymakers to ensure successful implementation of vaccination programs in the United States.