© 2019 Studies with prophylactic HPV vaccination have demonstrated impressive efficacy, immunogenicity, and safety results; however, the implementation and uptake in both low and high-income countries continues to be challenging. Since 2006, administration guidelines have undergone multiple updates regarding age, dosing schedule, and gender. Despite these changes, the basic tenet remains the same: prioritize immunization before initiation of sexual activity and subsequent exposure to HPV. The importance of immunizing males and females equally and the role for catch-up vaccination in late adolescent and adulthood has also been supported by subsequent research. Very recently, the FDA approved to expand the range of eligible patients for the nonavalent (9vHPV) vaccine to women and men from age 27 to 45 for the prevention of HPV-related cancers and diseases. Furthermore, members of the ACIP voted to recommend that individuals between ages 27 and 45 who have not yet been vaccinated discuss the option with their physician. This review will highlight the history of the vaccine, barriers to vaccination, current recommendations, and future directions for success.