We are now in the fortunate position of having two highly promising human papillomavirus (HPV) vaccines in the pipeline. Amidst the excitement of anticipating what these vaccines may be able to offer, it is worth pausing to look back at how the vaccine development story unfolded from an industrial perspective, since without the massive commitment shown by manufacturers over the last decade, without any guarantee of success, there would be no such prospect. This chapter focuses on the two HPV prophylactic vaccines, produced independently by Merck & Co., Inc. and GlaxoSmithKline (GSK), that are in advanced clinical development, and it aims to provide an insight into the key considerations for initiating the programmes in a commercial context as well as some of the research and development hurdles that needed to be surmounted to bring them to the point where efficacy has been demonstrated and the licensing process is well underway.