Malaria is a deadly disease that can be managed with an efficacious vaccine. However, developing anti-malarial vaccines has been a complex and challenging process due to certain inherent characteristics of the Plasmodium parasite, the complexity of the parasite biology, and the disease. These notwithstanding, anti-malarial vaccine development efforts have been ongoing for several decades, with various innovative approaches that target multiple stages of the parasite’s life cycle, either in the secondary human or the primary mosquito host being explored. These efforts have so far led to the development of RTS,S/AS01, a subunit vaccine based on the circumsporozoite protein of the parasite through the GlaxoSmithKline and PATH Malaria Vaccine Initiative partnership. Following extensive clinical trials with RTS,S/AS01, the results revealed only moderate efficacy in reducing malaria episodes in young children and infants in Africa. This, notwithstanding, the World Health Organization approved RTS,S/AS01 as the first malaria vaccine followed by R21, developed by the University of Oxford, and marketed as R21/Matrix-M. Both vaccines work to prevent infection and are, therefore, being viewed as complementary tools to existing malaria control measures. Beyond these two, several other vaccine candidates are in various stages of development for improved efficacy, durability, and ease of administration.