The recognition that human papillomavirus (HPV) infection is the necessary cause of cervical cancer brought new prevention paradigms in screening and HPV immunization. We now face many questions about how to implement an ambitious evidence-based agenda for cervical cancer prevention. Much is known about the epidemiology and natural history of HPV infection but several key variables remain to be elucidated. Research on HPV transmission requires new study designs to provide useful insights into preventive strategies. HPV testing has carved a niche in clinical practice but to consolidate its role in screening still requires evidence of long-term benefit. The rapidly evolving field of HPV diagnostics has contributed useful information concerning the value of HPV typing. Other screening methods hold promise in specific settings. The decade-long process that brought HPV vaccines to the doorstep of public health application is over. Many questions remain concerning long-term efficacy, correlates of protection, age of vaccination, and delivery. As vaccination makes inroads as a cancer control strategy, screening practices must be reformulated to maximize the synergy between primary and secondary prevention. Research on how to achieve an efficient combination of these modalities is yet to begin, but mathematical models have provided a useful road map for field-testing of promising algorithms. Daunting questions loom large concerning delivery of vaccines to those populations that need it the most. The field of HPV and cervical cancer prevention has never been so multi-disciplinary. A new era has begun and the challenges are many.