Vaccination of young teenage females against human papillomavirus (HPV) with a newly licenced quadrivalent vaccine designed to prevent cervical cancer and genital warts has recently been recommended by the Australian government and will be implemented through schools from April 2007. In addition, a fully funded 'catch-up' vaccination program for young women up to age 26 years has been approved for a 2-year period, from July 2007. As general practitioners (GPs) will be the main immunisation providers for this age group, in order to achieve high vaccination coverage and maximal impact on disease, it will be critical for GPs to be opportunistic in recommending this vaccine. An initial study of young Australians' attitudes towards HPV vaccination and hypothetical acceptance of the vaccine was published in this journal. We draw on this study and data published elsewhere to discuss issues of HPV vaccine acceptability, and the likely challenges of a mass vaccination initiative in this age group in Australia. We suggest specific strategies to support GPs, and highlight areas for further research in HPV vaccine acceptability.