In sub-Saharan Africa (SSA), cervical cancer is a critical public health issue; it is the second leading cause of cancer among women and the leading cause of female cancer deaths. Incidence and mortality rates are substantially higher than in high-income countries with population-based screening programs, yet implementing screening programs in SSA has so far proven to be challenging due to financial, logistical and sociocultural factors. Human Papillomavirus (HPV) vaccination is an effective approach for primary prevention of cervical cancer and presents an opportunity to reduce the burden from cervical cancer in SSA. With a number of SSA countries now eligible for GAVI support for vaccine introduction, it is timely to consider the factors that impede and facilitate implementation of vaccine programs in SSA. This article reviews the epidemiological and clinical features of cervical cancer in SSA and describes the current status of HPV vaccine implementation in SSA countries. The review considers the challenges that will need to be addressed, and effective approaches to the design and implementation of HPV vaccination programs, using Rwanda as a case study. The review aims to provide suggestions and guidance to those involved in the development and implementation of HPV vaccination programs in SSA.