Malaria vaccine development aims to significantly reduce mortality and morbidity in the two high-risk groups: young children and pregnant women in sub-Saharan Africa. A pre-erythrocytic subunit vaccine, RTS,S, was recently evaluated in a first Phase IIb clinical trial in young children that live in a mesoendemic area of malaria transmission. The identification of a major parasite-encoded ligand that was found to be involved in pregnancy-associated malaria allows for the rational development of a tailor-made subunit vaccine for young women. The generation of transgenic yellow fever viruses and defined attenuated vaccine lines by reverse genetics are complementary approaches that might further boost the development of safe vaccines that elicit protective immune responses in this population.