Despite national guidelines and proven health benefits, vaccination rates for the human papillomavirus (HPV) remain far below those of other vaccines recommended for adolescents. HPV is the most common sexually transmitted infection in the U.S; it is responsible for about 25,000 new cancers each year. A series of three shots is recommended for all girls and boys at age 11-12, but significant barriers exist to starting and finishing this series. This Issue Brief examines some of the barriers and summarizes a successful, multipronged clinical intervention to improve vaccination rates.