The development and implementation of a malaria vaccine would constitute a major breakthrough for global health. Recently, numerous new candidates have entered clinical testing, following strategies that are as diverse as the malaria cycle is complex. While promising results have been obtained, some candidate vaccines have not fulfilled expectations. The challenges are not merely scientific; further progresses will require the development of competent investigator networks, partnerships between academics, industry and funding agencies, and continuous political commitment. In this review, we present the developmental status of all malaria vaccine candidates that are currently in human clinical testing against Plasmodium falciparum, as well as selected malaria vaccine candidates at preclinical development stage, and discuss the main challenges facing the field of malaria vaccine development.