Cervical cancer is responsible for one-quarter of a million deaths per year worldwide. In South Africa (SA), cervical cancer is the leading cause of cancer deaths among women aged 15-44 years. Human papillomavirus (HPV) vaccines provide a safe and highly effective means to reduce the burden of cervical cancer. The World Health Organization initiated a plan for the elimination of cervical cancer; the programme’s success relies on the introduction and high uptake of HPV vaccines globally. SA introduced a school-based HPV vaccination programme in 2014, but uptake is not as high as expected. Suboptimal HPV vaccination coverage may result from various factors, including vaccine hesitancy. Vaccine-hesitant parents may delay or refuse HPV vaccination for their daughters. Tailored interventions are needed to address this. However, knowledge regarding vaccine hesitancy and policies to address this hesitancy in SA are currently limited. While SA has taken commendable steps in cervical cancer prevention by implementing and financing the HPV vaccination programme, it is imperative that there are clear policies in place to help strengthen the programme. These policies need to clarify areas of uncertainty that may lead to mistrust, and pre-empt factors that will cause hesitancy. Equally important is that local research should be conducted to better understand HPV vaccination hesitancy and other determinants of uptake to further inform and shape national policies.