Clinical development of malaria vaccines has had remarkable achievements in the past decade, but an efficacious vaccine is yet to be licensed. There are many scientific and technical challenges that hamper progress ranging from parasite to host to technical and to mere traditional convention factors. This paper outlines some of the key issues along the pathway and proposes the need for much earlier phase clinical research within Africa suggesting rationale and ethical justification for doing so. Challenge model studies could particularly be employed within malaria endemic country settings which may have critical advantages to complement the currently available sites in developed countries.